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Motivational views of reinforcement: implications for understanding
the behavioral functions of nucleus accumbens dopamine
John D. Salamone *, Mercè Correa 1
Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA
Received 5 August 2001; accepted 27 June 2002
Abstract
Although the Skinnerian ‘Empirical Law of Effect’ does not directly consider the fundamental properties of stimuli that enable
them to act as reinforcers, such considerations are critical for determining if nucleus accumbens dopamine systems mediate
reinforcement processes. Researchers who have attempted to identify the critical characteristics of reinforcing stimuli or activities
have generally arrived at an emphasis upon motivational factors. A thorough review of the behavioral literature indicates that,
across several different investigators offering a multitude of theoretical approaches, motivation is seen by many as being
fundamental to the process of reinforcement. The reinforcer has been described as a goal, a commodity, an incentive, or a stimulus
that is being approached, self-administered, attained or preserved. Reinforcers also have been described as activities that are
preferred, deprived or in some way being regulated. It is evident that this ‘motivational’ or ‘regulatory’ view of reinforcement has
had enormous influence over the hypothesis that DA directly mediates ‘reward’ or ‘reinforcement’ processes. Indeed, proponents of
the DA/reward hypothesis regularly cite motivational theorists and employ their language. Nevertheless, considerable evidence
indicates that low/moderate doses of DA antagonists, and depletions of DA in nucleus accumbens, can suppress instrumental
responding for food while, at the same time, these conditions leave fundamental aspects of reinforcement (i.e. primary or
unconditioned reinforcement; primary motivation or primary incentive properties of natural reinforcers) intact. Several complex
features of the literature on dopaminergic involvement in reinforcement are examined below, and it is argued that the assertions that
DA mediates ‘reward’ or ‘reinforcement’ are inaccurate and grossly oversimplified. Thus, it appears as though it is no longer tenable
to assert that drugs of abuse are simply turning on the brain’s natural ‘reward system’. In relation to the hypothesis that DA systems
are involved in ‘wanting’, but not ‘liking’, it is suggested in the present review that ‘wanting’ has both directional aspects (e.g.
appetite to consume food) and activational aspects (e.g. activation for initiating and sustaining instrumental actions; tendency to
work for food). The present paper reviews findings in support of the hypothesis that low doses of DA antagonists and accumbens
DA depletions do not impair appetite to consume food, but do impair activational aspects of motivation. This suggestion is
consistent with the studies showing that low doses of DA antagonists and accumbens DA depletions alter the relative allocation of
instrumental responses, making the animals less likely to engage in instrumental responses that have a high degree of work-related
response costs. In addition, this observation is consistent with studies demonstrating that accumbens DA depletions make rats
highly sensitive to ratio requirements on operant schedules. Although accumbens DA is not seen as directly mediating appetite to
consume food, principles of behavioral economics indicate that accumbens DA could be involved in the elasticity of demand for
food in terms of the tendency to pay work-related response costs. Future research must focus upon how specific aspects of task
requirements (i.e. ratio requirements, intermittence of reinforcement, temporal features of response requirements, dependence upon
conditioned stimuli) interact with the effects of accumbens DA depletions, and which particular factors determine sensitivity to the
effects of DA antagonism or depletion.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: Reward; Activation; Ergonomics; Fatigue; Incentive salience; Striatum; Motivation
* Corresponding author. Tel.: /1-860-486-4302; fax: /1-860-486-2760
E-mail address: [email protected] (J.D. Salamone).
1
Present address: Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12079 Castelló, Spain.
0166-4328/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.
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J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
1. Introduction
2. DA Hypothesis of reinforcement
One of the most intense and dynamic areas of
research in behavioral neuroscience is the study of the
functions of brain dopamine (DA). DA has been
implicated in several disorders, including schizophrenia,
depression and Parkinson’s disease. Moreover, the
dominant paradigm in drug abuse research has been,
for the past several years, the hypothesis that DA is the
critical neurotransmitter for the mediation of reinforcement phenomena. The DA hypothesis of ‘reward’ or
reinforcement has become one of the most ubiquitous
and popular hypotheses in the history of neuroscience.
Virtually every textbook in neuroscience, psychopharmacology or physiological psychology makes reference
to the DA hypothesis of reinforcement, and one can
easily find statements in support of this hypothesis on
the world wide web, or in the popular press. For
example, in an article in Newsweek magazine (12
February 2001), it was stated that ‘‘the pleasure
circuit communicates in the language of dopamine’’ (p.
40). In a popular university-level textbook [29], it
declares authoritatively that ‘‘Reinforcement occurs
when neural circuits detect a reinforcing stimulus and
cause the activation of dopaminergic neurons in the
ventral tegmental area’’ (p. 363). In a recent review
article, nucleus accumbens was referred to as the
‘Universal Addiction Site’ [48]. Indeed, the DA hypothesis of reward is no longer merely a testable scientific
hypothesis, and instead has become a widely promoted
dogma.
In the last few years, several papers have provided
critical evaluations of the DA hypothesis of reinforcement [18,93,114,128,154,155,157,160,165,193]. The present review is intended to have a different focus than
most previous papers. The hypothesis that DA is
involved in reinforcement presupposes that scientists
understand or agree upon what the term ‘reinforcement’
actually means. In the present paper, we will argue that
the particular model of reinforcement that one employs
is of critical relevance for interpreting the literature on
dopaminergic involvement in reinforcement. In summarizing various views of reinforcement, it will be
suggested that learning and motivational processes are
two critical aspects of reinforcement, and particular
emphasis will be placed upon the fundamental importance of motivational factors for reinforcement processes involving natural stimuli such as food. Finally,
this article will review the literature on aspects of
motivation that are relatively preserved after interference with DA systems, and will discuss why such
preserved functions render the DA hypothesis of
reinforcement inadequate as a global theoretical framework.
Several researchers are associated with the DA
hypothesis of reinforcement, but the person most widely
credited for the formal inception of this hypothesis is
Wise (e.g. [215,216,218,219,223,224] but see also
[217,222] for a more recent re-appraisal by this author).
According to this hypothesis, DA systems mediate the
reinforcing effects of several different classes of stimuli.
The DA hypothesis of reinforcement was offered to
explain the neural mechanisms underlying intracranial
self-stimulation [215], and was eventually extended to
include natural reinforcers such as food, water and sex,
as well as drugs of abuse [218,219,223,224]. Of course,
no serious scientist would maintain that brain DA
systems evolved so that mammals could abuse drugs
and respond to electrodes; thus, a fundamental aspect of
the DA hypothesis of reinforcement is that DA neurons
constitute a critical link in the brain’s natural reinforcement system, which evolved to mediate reinforcing
effects of natural stimuli such as food. In turn, it is
maintained that reinforcing brain stimulation and
rewarding drugs of abuse activate the natural reinforcement system in the brain by interacting with dopaminergic neurons and synapses.
The hypothesis that DA systems mediate the reinforcing value of natural stimuli, electrical stimulation and
drugs of abuse has been referred to as the General
Anhedonia Model [165]. It should be pointed out that
the preponderance of the work in this area has focused
upon the reinforcing effects of drugs of abuse. Nevertheless, the present review will focus on natural reinforcers, especially food. This is important in view of the
conceptual structure of the General Anhedonia Model.
Because it is argued that drugs of abuse turn on the
brain’s natural ‘reward system’, studies of the role of
DA in reinforcement processes related to food and other
natural stimuli are essentially the linchpin of the General
Anhedonia Model. Often, it is simply assumed that DA
mediates food reinforcement, and there are sparse and
selective citations of research in this area; this notion is
rarely challenged or examined critically in the drug selfadministration literature. Nevertheless, several recent
papers have highlighted some of the difficulties with the
hypothesis that accumbens DA mediates reinforcement
for
natural
stimuli
such
as
food
[18,93,96,155,157,160,165,193]. Parkinson et al. [143]
noted that dissociations appear to exist between the
role of accumbens DA in behavior controlled by drug
and natural reinforcers, and stated that ‘‘differences
between the effects of drugs and natural reinforcers on
the brain might hold important keys to the etiology of
addiction’’ (p. 384). Thus, the present review will focus
on various views of reinforcement phenomena that have
emerged from the literature dealing with natural reinforcers. The hypothesis that DA systems directly
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
mediate food ‘reinforcement’ will be critically evaluated
in light of this literature.
3. What is reinforcement? The empirical law of effect
described
The modern study of instrumental conditioning is
built upon the seminal work of Thorndike and Skinner.
It was Thorndike (e.g. [197]), who invented the term
‘The Law of Effect’ to describe the processes involved in
instrumental conditioning. According to Thorndike, if a
response occurred in the presence of a stimulus, and this
led to a ‘satisfier’, then that response was likely to occur
again in the presence of the same stimulus. Thorndike
[197] maintained that responses ‘which are accompanied
or closely followed by satisfaction to the animal will,
other things being equal, be more firmly connected with
the situation’. A generation later, Skinner (e.g.
[181,182]) composed a more empirical form of the Law
of Effect, which simply and elegantly focussed on the
relation between response output and the stimulus
events that followed these responses. According to
Skinner, positive reinforcement occurs when a response
is followed by a stimulus, and response probability
increases. The stimulus that leads to such an outcome is
known as a positive reinforcer.
In contemporary psychology and neuroscience, it is
Skinner’s language and description that generally predominates. One rarely sees reference to the Thorndikian
terminology of ‘satisfiers’ and ‘annoyers’, except in
reference to historical developments in the field. In
contrast, the terms ‘positive reinforcement’, ‘negative
reinforcement’, and ‘reinforcer’ are ubiquitous in the
scientific and clinical literatures, as well as in the
classroom and the workplace. Skinner attempted to
devise a technology of behavior modification using
instrumental conditioning techniques, and also attempted to enunciate an empirically-based language of
behavior. In striving for these goals, Skinner was
enormously productive and successful. Nevertheless,
one of the issues that Skinner did not discuss in detail
was the characteristics of stimuli that allow them to act
as reinforcers. If one were to evaluate the claim that a
neurotransmitter such as DA mediates the effects of
reinforcing stimuli, then it would seem advisable to
review the literature on the critical characteristics of
reinforcing stimuli.
4. What are the critical characteristics of reinforcing
stimuli? Motivational and regulatory views of
reinforcement
Typically, when a student first learns about reinforcement, it is in the context of a course in ‘learning’. When
5
one wants to read about instrumental conditioning
procedures, or schedules of reinforcement, one often
looks in a book on ‘learning’. Moreover, anytime a
scholar wishes to learn more about Thorndike, Skinner,
Tolman, Hull, Spence, or various other researchers who
have studied instrumental behavior, this information is
typically discussed in terms of ‘Learning Theory’. Of
course, learning is a critical aspect of the acquisition of
new instrumental behaviors. Nevertheless, it is something of a misapprehension to place a selective emphasis
on learning, as opposed to other processes, when
studying instrumental behavior. Instrumental behavior
is a complex and multifaceted process, which involves
learning mechanisms, but also involves perceptual,
motor and motivational functions output [20,36,50,61].
It will be argued in this paper that research and
scholarship on the fundamental characteristics of reinforcing stimuli have inevitably led to an emphasis on
motivational factors, and that current behavioral theory
emphasizes a combination of associative and motivational processes to explain reinforcement phenomena.
Before discussing various views of reinforcement, it
would be useful to define the term ‘motivation’. As with
any psychological construct, motivation has been defined in several different ways. For the present paper, we
will employ a definition of motivation from some of our
earlier papers (e.g. [154,155]). According to this earlier
work, motivation is the set of processes through which
organisms regulate the probability, proximity and
availability of stimuli. This definition is intended to
involve the regulation of both internal and external
stimuli. As discussed below, motivated behavior typically takes place in phases, including a terminal or
consummatory phase in which the organism directly
interacts with the motivational stimulus, and also an
instrumental phase in which the organism regulates the
proximity or delivery of stimuli [154,155]. In addition,
motivation has both directional and activational aspects
[35,55,154,155,159,165]. Directional aspects of motivation refer to the fact that behavior is directed towards or
away from particular stimuli; activation refers to the
energetic aspect of motivated behavior, i.e. the vigor or
persistence. As noted by Cofer [34] ‘Motivational
concepts, then, have had at least two major functions
with respect to behavior. One is to energize responses,
either in general or specifically, and to control their
vigor and efficiency. The other is to guide behavior to
specific ends, i.e. to give direction to behavior’.
Although there are a number of distinct views of the
critical characteristics of reinforcing stimuli, there is a
common pattern that runs through much of the
psychological literature. According to several different
investigators, reinforcing stimuli act as motivational
stimuli; reinforcers are seen as goal stimuli towards
which behavior is directed, or as stimuli or activities that
are being regulated by the organism. For most of these
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J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
researchers, this was not some incidental or epiphenomenal characteristic of reinforcers; rather, this property
is viewed as a fundamental feature of reinforcement. As
noted above, Thorndike was the first researcher to study
the principles of instrumental conditioning in detail. In
discussing the characteristics of stimuli that can act as
satisfiers, Thorndike [197] stated that a satisfier is a
stimulus that ‘‘the animal does nothing to avoid, often
doing such things as to attain and preserve it’’. Thus,
although Thorndike often is cited as the founder of the
S-R learning school, and a precursor of the ‘responsereinforcement’ view of instrumental behavior (e.g. see
[21]), a close examination of his original work demonstrates that a satisfier was viewed by Thorndike as
having important motivational characteristics. Tolman
[200] emphasized that the demand for the ‘goal-object’
(i.e. the reinforcer) was a critical factor that promoted
maze learning. The concept of ‘need reduction’ was
important for Hull [88] as a fundamental condition for
reinforcement to occur. As indicated by his discussion of
Cannon’s work on homeostasis, it is evident that Hull
thought of instrumental behavior as a learned extension
of the general principle of homeostatic regulation [7],
which is clearly a motivational concept. Hull [88], and
later Spence [186] also emphasized the importance of the
‘incentive’ properties of reinforcers. Spence [186] summarized his view of the relation between reinforcement
and motivation by writing that ‘‘The combination of a
motivating state and the environmental situation impels
the subject to respond and to continue responding to
various aspects of the situation until a reinforcer is
obtained or until removed from the situation’’ (p. 29). In
a later work, Cofer [34] stated that ‘motivation provides
the conditions for reinforcing behavior or weakening it’.
As noted by Domjan and Burkhardt several years
later [54] ‘‘At present, it is convenient to think of all
sources of motivation as contributing to reinforcement
effects’’.
Although need reduction and drive reduction were
later discarded as the main mechanism through which
reinforcers were thought to act, these concepts were
replaced by other ideas that also were related to aspects
of motivation. Sheffield and Roby [180] observed that a
non-nutritive sweetener such as saccharine could act as a
reinforcer. According to these researchers, the critical
characteristic of a reinforcer, therefore, could not be
drive or need reduction. Rather, they suggested that
‘elicitation of the consummatory response’ is the critical
factor in determining the reinforcing characteristics of a
stimulus. This idea is closely related to the view of
Glickman and Schiff [71], who maintained that the most
important characteristic of a reinforcing stimulus is the
ability to instigate species-specific consummatory responses that help the organism adapt to its environment.
The person most widely credited with integrating
many of these diverse motivationally-based views of
reinforcement is Bindra. Bindra [21] built upon several
earlier concepts, including incentive, the importance of
goal-directedness, and the induction of consummatory
responses, to construct a view of reinforcement phenomena known as ‘incentive-motivation’. According to
Bindra [21], instrumental learning does not so much
reflect response-reinforcer associations as it does the
acquisition of stimulus-stimulus associations and the
modification of goal-directed responses. He suggested
that central motivational states influence the responseeliciting properties of stimuli, and that behavior initially
directed towards primary incentive stimuli (e.g. food)
can, through a perceptual learning process, be flexibly
redirected towards conditioned stimuli (e.g. the goal-box
or lever).
Some views of reinforcement characterize the reinforcer as an activity that is being regulated, as opposed to a
stimulus. In attempting to identify the principles that
allow activities to be used as reinforcers, Premack [147]
observed that reinforcers are activities that occur with a
relatively high probability, or are relatively preferred.
According to the principle that now bears Premack’s
name, a high probability activity (such as eating) can be
used to reinforce a low probability activity (such as lever
pressing). Another view of reinforcement based upon
behavioral regulation is referred to as response deprivation theory [6,198,199]. Reinforcing activities are described as being relatively deprived, and this deprivation
disturbs the normal response equilibrium; engaging in
the reinforced response is seen as restoring the response
equilibrium. Timberlake and colleagues (e.g. [145,199])
have built upon the notion of response deprivation
theory, and developed the ‘behavior systems’ approach.
According to this view, food reinforcement is clearly
seen in the general context of the behavioral systems
regulating food-searching and food-consuming behaviors. In recent years, economic models have been used
to describe instrumental conditioning phenomena. Reinforcers can be said to be ‘goods’ or ‘commodities’ that
are being procured. As stated by Lea [117] ‘‘reinforcers
and commodities are both classes of things that a
subject will do something to get’’ (p. 443). Consistent
with this emphasis on economic principles, instrumental
responding is seen as the ‘cost’ that is paid to obtain
access to these commodities. Staddon and Ettinger [190]
discussed economic models in their comprehensive
overview of instrumental behavior, and noted that the
‘preference structure’ of the environment is an important determinant of the reinforcing characteristics of
stimuli.
At this point, it should be emphasized that each of
these behavioral researchers offers a distinct view of
instrumental conditioning, and the purpose of this brief
review is not to provide details about any one theory, or
to contrast them seriously with each other. Moreover,
this review is not intended to obscure the distinction
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
between each of these different theoretical systems.
Rather, the overview provided above was meant to
show that, despite the differences between various
behavioral theories, a common principle emerges when
one considers the issue of the fundamental characteristics of reinforcing stimuli. The vast majority of
researchers who have pondered this issue have arrived
at the conclusion that appetitive motivation is critical
for the process of positive reinforcement. According to
Tapp [195] ‘‘At the simplest level, reinforcers have the
capacity to direct an organism’s behavior. Those stimuli
that are approached are regarded as positively reinforcing. . .’’ For some researchers (i.e. Bindra), positive
reinforcement phenomena are largely explained by a
combination of appetitive motivation and classical
conditioning. In contemporary learning theory, motivational and response-reinforcer associative mechanisms
are seen as jointly determining the acquisition of
instrumental behavior. For example, Timberlake [199]
emphasizes that response deprivation determines which
activities have reinforcing characteristics, but the organism must still learn ‘what leads to what’. Dickinson and
Balleine [50] emphasized the importance of motivational
factors in regulating goal-directed instrumental actions,
and also stressed the importance of learning about the
contingency between the instrumental action and the
goal or outcome. Thus, it can safely be said that, for a
wide variety of researchers who represent a broad
spectrum of opinions, appetitive motivation is a fundamental aspect of positive reinforcement. The reinforcer
can be described as a goal, a commodity, an incentive,
or a stimulus that is being approached, self-administered, attained or preserved. Reinforcers have been
described as activities that are preferred, deprived or
in some way being regulated. Nevertheless, despite the
rich variety of descriptive phrases being used, these are
different ways of emphasizing the same, overriding,
motivational principle. This fundamental motivational
characteristic of reinforcing stimuli is sometimes referred to as the primary (or unconditioned) reinforcing,
or primary incentive property of those stimuli [136,191].
5. The empirical law of effect revisited: motivational
corollary of the empirical law of effect
As noted above, Skinner did not invest a great deal of
effort in discussing the critical characteristics of stimuli
that allow them to act as reinforcers. Indeed, if one’s
goal is to develop a system of behavioral control using
operant conditioning, the fact that a stimulus is reinforcing may be more important than why it is reinforcing.
Nevertheless, it is useful to consider the relation between
the motivational or regulatory views of reinforcement
described above and Skinner’s Empirical Law of Effect.
7
First of all, it is important to recognize that Skinner did,
on occasion, consider the role of motivational variables
such as food deprivation in the process of reinforcement.
For example, Skinner [180] stated ‘‘Reinforcement thus
brings behavior under the control of an appropriate
deprivation. After we have conditioned a pigeon to
stretch its neck by reinforcing with food, the variable, which controls the neck-stretching, is food deprivation’’.
Designed as it was to allow for control of the behavior
of organisms, the Empirical Law of Effect was oriented
from the perspective of the one doing the controlling, i.e.
the experimenter. In contrast, the motivational or
regulatory view is oriented from the perspective of the
organism. According to the Empirical Law of Effect, the
experimenter presents the reinforcer after a response
occurs and observes an increase in response rate.
However, if there is a contingent relation between the
response and the reinforcer, then it must also be true
that there is an increase in reinforcer delivery that
accompanies the increase in response probability. In
summarizing Thorndike’s experiments, Rachlin [148]
stated that, after the organism was reinforced, ‘‘This,
in turn, increased the likelihood of the behavior
recurring and producing more rewards’’ (p. 75, my
italics). Thus, consistent with what has previously been
described as a motivational corollary of the Empirical
Law of Effect [155,165], a reinforcer can be described as
a stimulus that is increased in probability by the
organism. This observation was an attempt to bridge
the apparent gap between the Law of Effect and the
motivational or regulatory views of reinforcement. In
taking both the Law of Effect and the regulatory view of
reinforcement into account, it can be said that instrumental behavior is characterized by a complex
organism /environment system, in which the environment shapes the behavior of the organism, but the
behavior of the organism, in turn, regulates environmental events. To take the example from Skinner, noted
above, it may be true that food deprivation controls the
reinforced operant of neck-stretching, but it also is true
that neck-stretching controls the delivery of food, and
ultimately, regulates the deprivation itself. Indeed, the
main adaptive value of instrumental behavior processes
to the organism is that these processes allow the
organism to regulate its environment, making some
stimuli proximal, or some activities possible, while
avoiding, delaying or escaping others. These behavioral
processes have adaptive value for the organism in the
sense that patterns of behavior are selected in relation to
the consequences of the instrumental actions emitted by
the organism, which would compliment and extend the
epigenetic mechanisms of adaptive behavior naturally
selected by evolutionary processes [188].
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J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
6. The importance of motivational concepts for the
dopamine hypothesis of reinforcement
In the prefatory remarks that began this article it was
suggested that, for evaluating the DA hypothesis of
reinforcement, it is important to identify the particular
model or definition of reinforcement being employed. A
careful examination of the literature shows that the
motivational view of reinforcement has had a powerful
influence over the DA/reinforcement hypothesis.
Although some researchers have emphasized the effect
of DA antagonists or depletions on response-reinforcement associative processes, in general, proponents of the
DA/reinforcement hypothesis have used some form of
the motivational view of reinforcement. For several
decades, Wise emphasized a motivational interpretation
of the effects of DA antagonists. For example, Wise et
al. [223] stated that pimozide suppressed operant lever
pressing for food because this DA antagonist took the
‘goodness’ out of the food. In explaining the effects of
DA antagonists on schedules supported by intermittent
reinforcement, Gray and Wise [76] cited Bindra’s work
on incentive motivation to provide background for their
position. Emphasis on motivational effects of DA
antagonists and DA depletions was evident throughout
a review by Wise published in 1982 [219]. In a
subsequent review Wise [218] explicitly identified his
view of instrumental behavior as being one very similar
to Bindra. Wise ([218], p. 183) stated that he did not
believe the ‘response-reinforcement’ view of instrumental behavior, but instead emphasized Bindra’s incentivemotivation view. Thus, in discussing the effects of DA
antagonists on instrumental behavior, Wise ([218], p.
183) stated that ‘‘What is important here is the nature of
the unconditioned responses to a rewarding stimulus, for
I worded my statements of the anhedonia hypothesis to
imply that neuroleptics block these responses. . .’’ (my
emphasis added). Consistent with this conceptualization
of reward as based upon primary motivation, it should
be emphasized that several researchers who support the
DA hypothesis have employed measures of consummatory behavior to study the putative effects of DA
antagonists on ‘reward’. These measures include food
intake
[220,221]
and
sucrose
consumption
([135,174,226]; see review in [184]). Berridge and Robinson [18] maintain that DA systems are necessary for
aspects of incentive motivation related to appetite, and
also emphasize the importance of ‘consumption tests’ as
a measure of reward (p. 313).
In discussing the hypothesized motivational functions
of DA, some researchers have focussed upon emotional,
or hedonic aspects of motivation. Thus, the term
‘anhedonia’ was meant to signify that DA antagonists
suppressed reinforced behavior because they blunted the
hedonic impact of pleasurable stimuli [219]. This notion
also has been popular in the drug abuse literature. For
example, Gardner [68] stated that ‘‘the mesotelencephalic DA system almost certainly serves as an important
substrate for the encoding in the brain of hedonic value
imparted by abusable substances’’ (p. 88). Yet, the
notion that interference with DA systems causes ‘anhedonia’ is highly controversial. In the drug abuse
literature, the work of Gunne [77] often is cited, because
this study suggested that the euphoric effects of amphetamine could by blocked by DA antagonism. Yet,
subsequent research has challenged this notion. For
example, Gawin [70] reported on four cocaine users who
were prescribed DA antagonists because of their paranoid reactions to the drug. According to Gawin [70]
‘‘The patients reported continued euphoria from cocaine
readministrations and lengthened cocaine binges because the dysphoric paranoia that often forced an end to
their drug use did not occur’’. Brauer and De Wit [24]
also noted that pimozide failed to blunt amphetaminestimulated euphoria. More recently, the novel D1
antagonist ecopipam failed to blunt the self-administration and the subjective euphoria reported to be induced
by cocaine [79,137]. Regardless of whether or not future
research demonstrates clear dopaminergic involvement
in the pleasure produced by some drugs of abuse, it
remains true that studies of reactivity to food are
certainly problematic for the General Anhedonia
Model. Considerable research with the taste reactivity
paradigm has demonstrated that interference with DA
by systemic administration of DA antagonists or by
local depletions of DA in nucleus accumbens or
neostriatum failed to alter appetitive taste reactivity
for sucrose [16,18,204]. This has led Berridge, Robinson
and colleagues to conclude that brain DA does not
mediate ‘liking’ (i.e. the hedonic reaction to food).
Nevertheless, these authors have suggested that DA
may be involved in ‘wanting’ food (i.e. incentive salience
of food, or the ‘appetite’ for food; see discussion below).
Although the motivational or regulatory view of
reinforcement seems to be the predominant view employed by advocates of the DA/reinforcement hypothesis, this is not universally true. Ettenberg and
colleagues (e.g. [31,83,131]) have taken the perspective
that interference with DA systems does not impair
primary motivation for reinforcers, but does impair
reinforcement. In these studies, the task used to identify
the ‘reinforcement’ function being disturbed is the
reinstatement of responding after extinction. Thus, for
Ettenberg and his colleagues, reinforcement can be
defined simply by the effect of a reinforcer on subsequent behavior. Essentially, this argument is based upon
a definition of reinforcement that solely involves response-reinforcement associations, and not motivational
processes. Such a view is rather unique, because most
advocates of the DA hypothesis of reinforcement rely
heavily upon the motivational view of reinforcement
processes. Nevertheless, in the context of the present
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
paper it also should be pointed out that, based upon
results from their own paradigm, Chausmer and Ettenberg [32] concluded that accumbens DA did not mediate
reinforcement as measured by the response-reinstatement paradigm.
In some sense, there appears to be a considerable
range of opinions as to what constitutes the ‘reinforcement’ or ‘reward’ process that is supposedly being
blunted by DA antagonists or depletions. Indeed, this
variability can make the scientific refutability of the
hypothesis quite difficult. Some investigators maintain
that DA antagonism does not blunt primary motivation,
but nevertheless impairs reinforcement processes, defined as the effect of a reinforcer on subsequent behavior
[131]. Several papers have offered a hedonically based
incentive-motivational view, and maintain that DA
antagonists blunt pleasure (e.g. [219,223,224]). Other
references seem to downplay the role of pleasure but
emphasize motivational aspects of reinforcing stimuli in
claiming that DA systems interfere with the incentive
motivation process (e.g. [217,218]). Additional work
argues forcefully against the position that DA systems
mediate pleasure, but argues in favor of dopaminergic
involvement in aspects of incentive motivation related to
appetite and reinforcer consumption (i.e. ‘wanting’;
[18]). Yet despite the wide variety of theoretical perspectives being offered, it should be recognized that a
majority of papers offering support for the DA hypothesis of reward or reinforcement seem to provide a view
of instrumental behavior processes that is consistent in
some way with the motivational view of reinforcement
[17,18,184,187,214,219,223,224].
7. Dissociable aspects of reinforcement and motivation:
on the role of accumbens dopamine
In the pages above, evidence was reviewed indicating
that motivation is seen by many investigators as a
critical, even defining feature of the effects of reinforcing
stimuli. Moreover, it is evident that most proponents of
the DA hypothesis of reinforcement not only adhere to
this view, but also actively employ it as an explanation
of the impairments induced by DA antagonists. Thus, in
evaluating the DA hypothesis of reinforcement, it is
crucial to consider the effects of dopaminergic manipulations on various aspects of food motivation. In order
to provide a detailed focus on particularly relevant areas
of this vast literature, one question will be addressed
initially. Are the suppressive effects of low doses of DA
antagonists or accumbens DA depletions on steady-state
food-reinforced operant behavior due to reductions in
directional aspects of primary food motivation?. Essentially, this was the claim that was offered by Wise and
colleagues in the early, formative years of the DA/
reward hypothesis [219,223,224]. These early papers are
9
still cited in the contemporary literature as providing
critical evidence in support of the General Anhedonia
Model. Smith [184], who claimed to offer ‘proof’ of the
DA hypothesis of reward, maintains that suppression of
sucrose intake by DA antagonists is a key marker of
these reward functions. Why are low doses of neuroleptics being emphasized? It is evident to most proponents
of the DA/reward hypothesis that higher doses of DA
antagonists cause motor problems that severely impair a
number of different types of behavior (e.g. [218]).
Nucleus accumbens is receiving particular attention
because most researchers recognize the important motor
functions played by the neostriatum, and also because
this structure has often been cited as the critical
anatomical locus for the putative reward functions of
DA (e.g. [51,82,184]). Accumbens DA depletions severely alter self-administration of stimulants (e.g. [26]),
and this evidence is frequently cited as providing
essential support for the General Anhedonia Model;
this makes an assessment of the effects of accumbens
DA depletions on food motivation particularly crucial.
Finally, it must be stressed that, as noted above,
motivation is seen as having both directional and
activational components. When referring to the hypothesized motivational functions of DA, proponents of
the hypothesis that DA mediates ‘reward’ are clearly
emphasizing directional aspects of motivation. This is
not to say that activational aspects have been completely
ignored; Wise has written about ‘motivational arousal’
and ‘energizing’ effects of rewards (e.g. [217,222]).
Nevertheless, the statements that DA antagonists take
the ‘goodness’ out of food, or blunt the ‘hedonic’ or
‘reward’ value of sucrose, or suppress the appetite for
food, or impair the unconditioned responses to food, are
certainly not emphasizing the involvement of DA in
activational aspects of food motivation, but rather are
stressing that DA is thought to be involved in the
process of directing behavior towards the acquisition
and consumption of food. After addressing the initial
question on the behavioral effects of low doses of DA
antagonists and accumbens DA depletions, the discussion will be broadened to include other brain areas and
additional behavioral functions.
7.1. Preserved aspects of motivational functions after
injections of low doses of DA antagonists and accumbens
DA depletions
If low doses of DA antagonists suppress lever pressing
for food because they produce a broad or general
reduction in food motivation, or appetite, or the
primary reinforcing or primary incentive properties of
food, then reductions of food intake, perceived reward
magnitude, or other behavioral markers of diminished
motivation should be evident in the same dose range as
the suppression of lever pressing. Yet, the literature
10
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
Table 1
Evidence against the DA/reward hypothesis: aspects of natural
motivation, reward or reinforcement that are preserved after accumbens DA depletion or antagonism
Little or no effect on fundamental aspects of motivation
Free food intake
[10,11,111,168,207]
Detailed parameters of time spend feeding, [168]
rate of feeding, forepaw usage during feeding, food intake
Approach to a estrous females, maze choice [89]
of estrous females, and execution of copulation
Lever pressing for food in low rate operant [1,26,41,57,127,150,166]
schedules: CRF, VI30 s
Discrimination of Reinforcement Magnitude [125,162]
Taste reactivity for sucrose
[16,18,19]
Lack of similarity of accumbens da depletions to effects of motivational
manipulations
Extinction
[127,130,160,166,167]
Pre-feeding
[1,160,166,169]
shows clearly that this does not occur (see Table 1 for
summary). It has been demonstrated repeatedly that DA
antagonists substantially impair lever pressing for food
at doses lower than those that suppress food intake or
simple approach responses for food [63,151,152,156].
Similar effects have been reported for water reinforcement as well [84,120/122]. These results are consistent
with many findings from diverse laboratories, which
have involved several different behavioral procedures,
instrumental responses and reinforcers. There are several previous reports indicating that doses of DA
antagonists that impair response rate measures of
behavior did not alter response choice measures
[23,42,59,156,162,201]. Instrumental responses with
very low response requirements are extremely resistant
to moderate/high doses of DA antagonists
[30,58,126,156], which demonstrates that the capacity
to reinforce some types of instrumental behavior is left
intact despite severe impairments in lever pressing that
can occur at these same doses. Martin-Iverson et al.
[125] used an operant psychophysical procedure to study
the effects of haloperidol, and reported that this DA
antagonist did not alter behavior in a way that is
consistent with a reduction in perceived reinforcement
magnitude (see also [108]). Agmo et al. [5] studied the
effects of DA antagonism on place preference, and
noted that although low doses of DA antagonists may
have affected associative processes, these low doses did
not affect sucrose consumption and thus ‘the reward
value of food or water was not reduced’.
The dissociative effects of low doses of DA antagonists on lever pressing versus food intake can clearly be
demonstrated in procedures that offer both activities
concurrently (see Table 2 for summary). Several studies
have been published employing concurrent lever pressing/chow feeding procedures, in which rats can lever
Table 2
Effects of DA manipulations on measures of instrumental response
choice
Decrease in lever pressing, increase in chow consumption
Increasing the ratio requirements
[165]
Systemic DA antagonism
Cis-flupentixol (non selective)
Haloperidol, Raclopride (D2)
SCH 23390, SKF 83566 (D1)
[47,161,164,169]
[47,161,164,169]
[47,161]
Intra-accumbens DA antagonism
Haloperidol, Raclopride (D2)
SCH 23390 (D1)
[141,169]
[141]
Accumbens DA depletions
6-OHDA
[44,45,169,185]
Decrease in lever pressing */decrease in chow consumption
Conditions that reduce appetite
Pre-feeding
Amphetamine
Fenfluramine
[169]
[41]
[161]
Conditions that produce severe motor impairments
Ventrolateral Striatal DA depletions
[45]
press on a continuous or FR5 schedule to receive a more
preferred food (Bioserve pellets), or can approach and
consume a less preferred food (lab chow) that is
concurrently available [42,44,45,169]. Typically, rats
under control conditions get the vast majority of their
food by lever pressing, and consume only small amounts
of chow. Behavioral research shows that the lever
pressing in this task is under control of motivational
factors; increasing the ratio requirement decreased food
acquisition through lever pressing and increased chow
consumption [165], while pre-feeding reduced both lever
pressing and chow intake [169]. Administration of
appetite suppressants such as amphetamine and fenfluramine also suppressed both lever pressing and chow
consumption [47,161]. Nevertheless, moderate to low
doses of DA antagonists produce a very different
pattern of effects. The non-selective DA antagonist cisflupenthixol, the D2 antagonists haloperidol, sulpiride
and raclopride, and the D1 antagonists SCH 23390 and
SKF 83566 all decrease lever pressing for food but
substantially
increase
chow
consumption
[47,110,161,164,169]. DA antagonism did not alter
consumption of or preference for these different foods
in free-feeding choice tests [169]. Thus, low doses of
neuroleptics that reduce lever pressing for food nevertheless leave the animal directed towards the acquisition
and consumption of food. Based upon all of these
studies, it seems untenable to argue that low doses of
DA antagonists suppress lever pressing for food reinforcement because they suppress appetite for food, or
broadly reduce directional aspects of food motivation.
Nucleus accumbens DA depletions induced by local
injections of 6-hydroxydopamine (6-OHDA) have gen-
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
erally been shown not to suppress 24 h food intake
[111,168,207]. Salamone et al. [168] studied the effects of
regional DA depletions on detailed parameters of chow
consumption. Nucleus accumbens DA depletions did
not suppress total chow consumed, total time spent
feeding, or the rate of feeding, nor did they alter forepaw
usage during feeding [168]. Bakshi and Kelley [10]
reported that intra-accumbens injections of haloperidol
did not suppress chow intake. Ikemoto and Panksepp
[92] demonstrated that intra-accumbens injections of the
DA antagonist flupenthixol reduced run speed for
sucrose reinforcement in a runway task, but did not
impair sucrose consumption. The concurrent lever
pressing/feeding task described above also has been
used to assess the role of DA in accumbens. Injections of
DA antagonists directly into the nucleus accumbens, or
DA depletions produced by local 6-OHDA injections,
have been shown to decrease lever pressing for food and
increase
chow
consumption
on
this
task
[44,45,110,141,169]. The nucleus accumbens often is
divided into core and shell subregions based upon its
anatomical organization [228]. The shift from lever
pressing to chow intake on the concurrent lever pressing/chow intake task occurred whether D1 or D2
antagonists, or 6-OHDA, were injected into the core
or the shell region [141,185], although with 6-OHDA
injections stronger effects occurred after core infusions
[185]. Taken together, these data demonstrate that
depletions of DA in nucleus accumbens do not generally
impair directional aspects of food motivation, and
indicate that the suppression of lever pressing resulting
from those depletions does not result from a loss of food
motivation.
The shift in behavior away from lever pressing and
towards chow consumption that is seen in the concurrent lever pressing/chow feeding task after interference
with DA does not appear to be occurring simply because
of a shift from an ‘instrumental’ behavior to a ‘consummatory’ behavior. A T-maze choice task was developed to assess this possibility [162]. In this task, one arm
of the maze contained a high density of food on each
trial (four pellets), while another arm contained a low
density (two pellets); rats were tested on 30 trials per
day. If both arms were unobstructed, the rats consistently chose the high density arm on the majority of
trials, and this choice behavior was unaffected by a low
dose (i.e. 0.1 mg/kg) of haloperidol, or by accumbens
DA depletions. If rats were trained and tested with a 44
cm barrier obstructing the high density arm, rats under
control conditions still climbed the barrier on most trials
to obtain the high density of food. However, with the
barrier present, the low dose of haloperidol or depletion
of accumbens DA caused a dramatic shift in behavior,
such that choosing to climb the barrier in the high
density arm was substantially reduced, but rats nevertheless left the startbox, entered the low density arm,
11
and consumed the food [42,162]. Together with the
operant concurrent choice studies, the T-maze data
indicate that low doses of neuroleptics, or depletions
of accumbens DA, act on instrumental behavior in a
way that interacts strongly with task requirements. Rats
with impairments in dopaminergic function remain
directed towards the acquisition and consumption of
food, and their behavior is still under the control of
differences in reinforcement magnitude or quality.
Nevertheless, DA antagonists or depletions cause a shift
in terms of response allocation (i.e. which path to the
food is selected); rats shift away from lever pressing or
barrier climbing towards simple locomotion to and
consumption of the food.
The continuous reinforcement schedule (CRF or
FR1) is the most basic example of a simple schedule
supported by primary reinforcement. In view of the
hypothesized importance of nucleus accumbens DA for
reinforcement or ‘reward’, this schedule should be
highly sensitive to the effects of accumbens DA depletions. In fact, the CRF schedule is relatively insensitive
to the effects of depletions of DA in nucleus accumbens
[1,127,166]. There are some mild suppressive effects of
accumbens DA depletions on response rate, which occur
within the first 15 min of the session during the first few
days of testing after DA depletion [127,166]. In fact, the
temporal characteristics of these relatively minor effects
raises some interesting questions about the nature of the
behavioral impairments induced by accumbens DA
depletions. One of the most common claims made by
advocates of the DA/reward hypothesis is that interference with DA induces ‘extinction’, i.e. a withinsession decline in responding that resembles the effects
of withdrawal of reinforcement (e.g. [223]). According to
this view, an extinction-like effect is produced because
neuroleptic-treated animals experience a reduction in
reward value when they encounter the food, and they
cease responding as the session progresses when the
reward deficit has an impact on their motivation to
continue responding. At this point, it must be stated
emphatically that, although systemic neuroleptics produce within-session declines in responding, accumbens
DA depletions do not produce a pattern of effects that
resembles extinction with natural reinforcers such as
food. Injections of the DA antagonist flupenthixol into
nucleus accumbens also were shown to produce effects
that did not resemble extinction [15]. In extinction,
response rate starts out very high, and then gradually
declines over time. In stark contrast, rats with accumbens DA depletions tend to start out slow, and over the
course of the session they either maintain a slow, steady
rate of responding or get faster as time goes on
[127,166,167]. On the CRF schedule, rats with accumbens DA depletions responded at rates at or slightly
higher than normal, and higher than extinction, by the
end of the session [127,166]. It is not clear why an animal
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J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
with blunted primary reinforcement would respond
more than normal at the end of the session, or hold to
a steady rate of responding, after multiple encounters
with a reinforcer of a supposedly diminished quality or
magnitude. The CRF schedule should be particularly
prone to diminished experience of primary reward,
because this schedule offers the most opportunities for
encountering the reinforcer. The CRF schedule is
sensitive to the effects of extinction [166], and to the
effects of pre-feeding [1]. Yet, the CRF schedule is
relatively insensitive to accumbens DA depletions. Rats
with accumbens DA depletions continue to respond
throughout the session on the CRF schedule, which
indicates that primary food reinforcement is not diminished. These observations are consistent with the
broader literature showing that, across a broad range
of schedules and conditions, the effects of DA antagonists or DA depletions do not closely resemble the
effects of extinction [56,72,73,160,165,201,203].
The insensitivity of food-reinforced CRF responding
to the effects of accumbens DA depletions brings up
another important point. As a part of the logic of the
General Anhedonia Model, the involvement of accumbens DA in stimulant self-administration often is
attributed to the notion that accumbens DA is a critical
part of the natural ‘reward system’, which mediates food
reinforcement. Thus, it is suggested that drugs of abuse
act by turning on the ‘natural reward system’. Yet, it
should be emphasized that, in spite of the generally
severe alterations in stimulant self-administration that
are seen after accumbens DA depletions, these same
depletions have surprisingly little effect on food-reinforced responding on several schedules [26,57,150].
There are several factors that determine why some
food-reinforced tasks are affected by accumbens DA
depletions, while others are not. The response allocation
literature shows that accumbens DA depletions affect
the selection of vigorous instrumental responses if there
are other, less effortful alternatives available [165]. Shifts
in behavior away from FR5 responding or barrier
climbing, and towards alternative paths to reinforcement, occurred even though the accumbens DA depletions did not severely suppress FR5 lever pressing or
barrier climbing when no alternative sources of food
were available [42,44]. Another possible determinant of
the effects of accumbens DA depletions is the baseline
rate of lever pressing [160]. Thus, it is possible that
performance on some schedules (e.g. CRF, VI 30 s) is
relatively unimpaired because these schedules generate
relatively low baseline rates. An additional factor
influencing the effects of accumbens DA depletions is
the ratio requirement of the schedule. In one study, rats
were tested on FR1, 4, 16 and 64 schedules [1].
Accumbens DA depletions had no effect on FR1
performance and had only transient effects on the FR4
schedule. More substantial impairments were shown
with the FR16 schedule, while FR64 responding was
severely impaired. Severe impairments in responding
also were shown by animals responding on very large
ratios, such as FR200 and FR300 [170]. These results
indicate that accumbens DA depletions enhance ‘ratio
strain’ (see Section 7.5 below for more discussion on the
sensitivity of ratio schedules to the effects of accumbens
DA depletions).
If interference with DA systems blunted primary food
motivation, then the effects of DA antagonists or DA
depletions should closely mimic the effects of prefeeding to reduce food motivation, or should resemble
the effects of appetite suppressants. In fact, several
studies have demonstrated that the effects of DA
antagonists or DA depletions differ substantially from
the effects of pre-feeding. In terms of food intake, the
effects of haloperidol or forebrain DA depletions on the
patterns of eating (e.g. rate of feeding, time spent
feeding) differ substantially from the effects of prefeeding [171]. On the concurrent lever pressing/chow
feeding task, pre-feeding suppressed both lever pressing
and chow consumption, while DA antagonists and
accumbens DA depletions decreased lever pressing but
increased chow consumption [169]. The effects of DA
antagonists and accumbens DA depletions on concurrent lever pressing/feeding tasks do not closely resemble
the effects of the appetite suppressant, fenfluramine.
Fenfluramine, like pre-feeding, does not cause a shift
from lever pressing to chow feeding, but instead
suppresses food consumption from both sources [161].
More recently, the effects of accumbens DA depletions
and pre-feeding were compared with a variety of
different FR schedules (FR1, 4, 16 and 64) [1]. As
described above, the effects of accumbens DA depletions on lever pressing were highly dependent upon the
ratio requirement, with FR1 responding being unaffected, and greater impairments being observed as ratio
requirements of FR16 and FR64 were used. Yet,
although FR1 performance was unimpaired by DA
depletions, pre-feeding substantially reduced lever pressing on this schedule. Regression analyses demonstrated
that accumbens DA depletions a pattern of suppressive
effects across schedules that was quite different from the
effects of pre-feeding [1]. In addition, several studies
involving analysis of interresponse time (IRT) distributions have shown that accumbens DA depletions
produce a general slowing of the IRT distribution
[160,166,167], while extinction and pre-feeding produce
very different patterns [160,166].
In summary, interference with DA systems by administration of low doses of DA antagonists or by local
depletions of accumbens DA does not produce effects
that closely resemble the effects of extinction, prefeeding or appetite suppression produced by a variety
of pharmacological agents. Instead, interference with
DA systems leaves fundamental aspects of food motiva-
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
tion and primary food reinforcement intact. Consistent
with the motivational or regulatory view of food
reinforcement reviewed above, these data demonstrate
that food-reinforced lever pressing on some schedules
can be suppressed under conditions that leave the
primary, or unconditioned reinforcing properties (or
primary incentive properties) of food unimpaired. In
view of these findings, it seems inaccurate or overly
simplistic to summarize the effects of DA antagonists or
accumbens DA depletions by claiming that they block
primary ‘reward’ or ‘reinforcement’.
7.2. Feeding deficits produced by substantial challenges to
brain DA systems
In the passages above, it was emphasized that low
doses of DA antagonists, or accumbens DA depletions,
did not fundamentally block directional aspects of food
motivation. Of course, dopaminergic impairments can
disrupt food intake. Nevertheless, the preponderance of
evidence indicates that these effects occur with higher
doses DA antagonists, or with depletions in motor
related areas in neostriatum, and also that these feeding
deficits are accompanied by clear signs of motor or
sensorimotor disruption. For example, haloperidol can
suppress lever pressing substantially in doses lower than
0.1 mg/kg; in a recent article the ED50 for suppression
of FR5 lever pressing was reported to be 0.08 mg/kg
[206]. Studies of chow feeding indicate that higher doses
(e.g. 0.2 /0.4 mg/kg) are necessary for suppressing
feeding [171]. These higher doses of neuroleptics that
suppress feeding also suppress locomotor activity and
induce catalepsy [94,146]. Detailed examination of the
patterns of feeding indicate that the predominant effect
of pre-feeding is a reduction in time spent feeding
[39,171], while haloperidol has much greater effects on
feeding rate (i.e. feeding efficiency or grams of food
eaten per min spent eating; [171]). Several other DA
antagonists also suppress rate of feeding [22,33,40]. Rate
of feeding also is the primary marker of the impairments
in feeding shown by rats recovering from the effects of
forebrain DA depletions. In one study of recovery of
function, rats initially made aphagic by near-total
forebrain DA depletions were akinetic, and spent very
little time engaging in any activity, including feeding.
Yet, by the 2 week after surgery, despite the fact that
their total food intake remained dramatically impaired,
most DA-depleted rats spent more time feeding than
normal rats [171]. The impairment in feeding was due to
a substantially reduced rate of feeding and severe
alterations in forepaw and oral motor control [171].
Large forebrain DA depletions produce severe feeding
deficits [124], and on occasion this effect has been
attributed to the so-called ‘reward’ system of the nucleus
accumbens. For example, in figure 5 of [17] it is stated
that 6-OHDA lesions of the ‘mesolimbic DA projec-
13
tions’ produce aphagia. Nevertheless, the literature
shows that the anatomical locus at which DA depletions
impair eating is not the nucleus accumbens
[111,168,207]. Rather, it is the lateral neostriatum, or
more specifically, the ventrolateral neostriatum (VLS)
that is the site at which DA depletions or DA
antagonists severely disrupt food intake ([10,56,95,168]
see also [193]). Rats with VLS DA depletions have
severe deficits in feeding rate and forepaw usage during
feeding, which result in a substantial deficit in total food
intake that is not seen after DA depletions in other
areas, including the nucleus accumbens, the anteroventromedial striatum, or the dorsomedial striatum
[45,95,168]. Considerable evidence indicates that VLS
is involved in motor function, and that VLS DA
depletions produce a constellation of motor deficits
involving the head, orofacial and forepaw regions. For
example, lateral striatal DA depletions impair reaching
and grasping with the contralateral forepaw [153], and
induce tremulous movements of the jaw that have the
temporal characteristics of Parkinsonian tremor [64,95].
Anatomical evidence indicates that the lateral striatum
in general and the VLS in particular receive inputs from
sensory and motor areas of neocortex [132]. Interestingly, rats with VLS DA depletions, despite the severe
difficulties with skilled movements, remain directed
towards food intake. In spite of the profound impairments in feeding rate that were seen, time spent eating
was not reduced by VLS DA depletions [168]. Although
DA depleted rats are less successful than untreated rats
at reaching and grasping, rats with depletions of DA in
striatal areas that include VLS actually made more
attempts to grasp the food pellets than normal animals
[153]. Most of the rats with VLS DA depletions can
maintain their body weight by eating wet mash, and
often these rats are seen to devour the mash in a
vigorous, if somewhat uncoordinated manner if it is put
in front of them; only the most severely impaired rats
have to be tube fed [43,168]. Thus, there is no evidence
that VLS DA depletions impair feeding through a deficit
that is primarily motivational, while overwhelming
evidence indicates that these rats have impairments in
head, orofacial and forepaw motor control. The precise
nature of the impairments induced by VLS DA depletions are still being characterized. Motor activity counts
based upon gross locomotion tend to be normal, and it
is not clear if their fundamental problem is with the
execution of skilled motor acts, the parallel execution of
simultaneous actions, coordination, sequencing or sensorimotor integration [43,45,46,168]. Nevertheless, the
literature on the effects of VLS DA depletions does not
provide support for the hypothesis that primary food
reward is mediated by DA systems.
Sucrose drinking is another task that has been used to
measure the putative reward functions of DA
[17,18,141,174,184]. Smith [184] constructed an elabo-
14
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
rate ‘proof’ of the DA hypothesis of reward based
largely upon studies of sucrose drinking. In this article
Smith [184] discussed studies in which doses of 12 mg of
the D1 antagonist SCH 23390 were injected directly into
the nucleus accumbens, and claimed that the resulting
suppression of sucrose consumption reflected a blunting
of reward. In considering the relevance of these data for
operant conditioning effects, it should be emphasized
that doses of 75 mg/kg SCH 23390 injected IP suppress
lever pressing substantially [2]. In a 300 g rat, this dose
would be equivalent to an IP injection of 22.5 mg into the
gut. Thus, an intracranial dose that is relatively high by
comparison (e.g. 12.0 mg) hardly argues for anatomical
specificity of the D1 antagonist effect. In our laboratory,
the entire intra-accumbens dose-response curve for the
suppression of lever pressing by SCH 23390 is evident at
doses under 2.0 mg per side [205], and the entire doseresponse curve for the shift from lever pressing to chow
intake produced by this D1 antagonist is evident at
doses less than 1.0 mg per side [141]. Relatively high
doses of the D2 antagonist raclopride (e.g. 40.0 mg) also
have been injected into nucleus accumbens in some of
these studies [174,184], and these doses are much higher
than the 1.0 mg per side dose of raclopride that
suppresses lever pressing [141]. Smith [184] also makes
the argument that, because the local rate of licking is not
affected by DA antagonists, then this is prima facie
evidence that no motor effects of any type are occurring.
This spurious argument ignores certain basic features of
the literature. First of all, there is no evidence that the
oscillatory pattern of tongue movements involved in
drinking has a local frequency set by basal ganglia
mechanisms. In fact, evidence indicates that this frequency is set by brainstem pattern generators [213].
Cataleptic doses of DA antagonists have little or no
effect upon the local frequency of licking [65]. Nevertheless, a number of other parameters of oral motor
function are altered by systemic or intra-accumbens
injections of DA antagonists. Jones and Mogenson [97]
observed that intra-accumbens injections of low doses of
spiroperidol impaired lap volume and tongue extension
in a water licking task. Several additional motor
parameters related to licking are impaired by DA
antagonists, including lick force [65,66], lick duration
[65,66,74], and lick efficiency [87,173]. Striatal DA
depletions that severely affected lick force had only
slight effects on lick rhythm [183]. Hsiao and Chen [86]
demonstrated that the response requirement (i.e. height
of the spout) was an important determinant of the effect
of DA antagonists on drinking. In short, the literature
on dopaminergic involvement in sucrose drinking, like
the literature on chow consumption, demonstrates that
conditions that suppress sucrose drinking are accompanied by signs of motor dysfunction. These motoric
effects of high doses of DA antagonists, therefore, place
additional emphasis on studies that employed low to
moderate doses. Injections of up to 25 mg of flupenthixol
directly into nucleus accumbens slowed instrumental
run speed in an alleyway, but did not suppress sucrose
consumption [92]. More recently, it has been demonstrated that DA antagonists injected into nucleus
accumbens in low doses that impaired learning or
suppressed locomotion did not suppress sucrose consumption [11]. In the presence of such evidence, there is
little support for the notion that interference with DA in
nucleus accumbens results in deficits in the primary
reinforcing or primary incentive characteristics of sucrose, or that these supposed deficits underlie the effects
of DA antagonism on instrumental behavior.
In the literature dealing with suspected reward functions of DA systems there are two related conceptual
problems in terms of how motor functions of DA are
discussed. The first problem relates to what has been
called the ‘absolute dichotomy’ between reward function
and motor function [165]. Before discussing what this
refers to, it is first useful to say what this does not refer
to. Obviously, proponents of the General Anhedonia
Model recognize that DA is involved in motor functions, and according to the DA reinforcement hypothesis DA antagonists should produce both types of effects
(e.g. [218]). The term ‘absolute dichotomy’ between
reward functions and motor functions does not refer
at all to the notion that both types of effects can occur in
the same animal at the same time. Instead, this term
refers to the notion that the specific reward/reinforcement/motivational functions supposedly impaired by
DA antagonists are completely distinct from all aspects
of motor function. If one conceives of DA antagonists
as blunting ‘hedonia’ or ‘appetite’, then it is clear that
these terms are meant to be conceptually distinct from
aspects of motor function. Yet a problem with this
distinction is that a broader consideration of motivational functions leads one to recognize the overlap
between aspects of motor function and aspects of
motivation. For example, in describing the incentivemotivation concept, Bindra [21] discusses the production of instrumental behavior in terms of the ‘instigation
of action’. Yet, neurologists maintain that DA is
important for the ‘initiation of movement’. It is not
clear how different these concepts are, though one is
meant to have a meaning in a motivational context and
the other is clearly motoric, and although one is meant
to be ‘psychological’ and the other more ‘neurological’.
As noted above, motivational stimuli are conceived of as
having activational as well as directional aspects.
Obviously, the behavioral activation produced by conditioned or unconditioned motivational stimuli, or by
novelty, is related to both motor and motivational
functions [154,155,158,159,165]. In this context, it is
interesting to note that the words ‘emotion’ and
‘motivation’ are both derived from the Latin word
movere (to move).
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
A related problem is that researchers who emphasize
the supposed ‘reward’ functions of DA fail to confront
directly the wide variety of functions that can be
described as motor, and the diverse nature of the motor
impairments that can emerge with disruption of the
nervous system. In arguing against the notion that DA
antagonists produce motor ‘incapacitation’, the fact that
motor function is not a unitary phenomenon often is
ignored, and the subtle aspects of some motor dysfunctions often are overlooked. Various types of motor
dysfunctions can occur, including lower motor neuron
paralysis, upper motor neuron paralysis, cerebellar
ataxia, parkinsonian akinesia, and apraxia, all of which
are quite distinct from each other. It would be convenient for advocates of the DA hypothesis of reward if
interference with the basal ganglia simply produced
paralysis or simple incapacitation; yet, the basal ganglia
just have not cooperated. The DA synapses in accumbens and striatum are several junctions removed from
the alpha motor neurons themselves, and it is generally
agreed that the basal ganglia are diffuse regulators of
motor output [25,138,155,165]. Different aspects of
motor function are anatomically dissociable from each
other, so it is possible to observe that VLS DA
depletions impair skilled arm movements and orofacial
motor function but leave gross locomotion basically
spared [43,45,95]. The literature on the symptoms of
human parkinsonism, as well as studies with animal
models, are full of examples of subtle and paradoxical
manifestations of the motor sequelae of DA dysfunction. For example, although the within-session ‘extinction’ of responding has become an icon for proponents
of the DA hypothesis of reward, similar effects are seen
in the motor symptoms of parkinsonism. Haase and
Janssen [78] reported that the micrographia shown by
patients with neuroleptic-induced parkinsonism is characterized by a progressive worsening within a writing
session. They note that ‘‘An increasing degree of
narrowing of the writing from stanza to stanza is
particularly characteristic, and in typical cases the area
covered by the writing assumes the shape of an inverted
pyramid’’ (p. 43) [78]. These authors also report that the
intensity of finger tapping decreases within a session in
patients with neuroleptic-induced parkinsonism (p. 234).
Similarly, repeated compression of the hands in parkinsonian patients reveals progressively diminishing motor
output [175]. In rats, DA antagonists cause withinsession increments in response duration [118], and
within session decrements in lick force [49]. It should
be emphasized that parkinsonian patients are not
paralyzed, despite an array of motor dysfunctions.
Akinetic parkinsonian patients can respond to intense
stimulation by showing ‘paradoxical’ kinesia [176], a
phenomenon also demonstrable in rats with DA depletions (e.g. [99]). Researchers often use the term ‘sensorimotor’, as well as motor, to describe the functions of
15
DA in basal ganglia [119,196,208]. The notion that
interference with DA can blunt behavioral responsiveness to stimuli has been a very powerful one, and has
been employed to explain deficits in responsiveness to
tactile stimuli [124] eating [212], gating of the startle
response [192], and operant reinforcement ‘threshold’
measurements [165]. In discussing the effects of DA
antagonists on sucrose consumption, Muscat and Willner [135] noted that ‘The ‘dopamine hypothesis of
(sweet) reward’ may thus be a misrepresentation of
data derived from under limited conditions of reinforcement. The blunting of reward by DA antagonists may be
a specific case of a more general attenuation of the
influence of sensory stimuli over behavior’. In considering the cogent nature of this statement, the validity of
the use of the term ‘reward’ to describe the deficits
produced by DA antagonism or depletion can be called
into serious question.
In summary, the characteristics of the feeding deficits
produced by high doses of DA antagonists and neostriatal DA depletions do not closely resemble the
appetite suppression produced by pre-feeding. In contrast, there is clear evidence of dopaminergic involvement in several distinct aspects of motor/sensorimotor
function that are important for feeding. Although rats
with impaired DA function are not paralyzed, and tend
to show normal lick frequencies, they do have problems
with lick force, lick duration, lap volume, tongue
extension, reaching, grasping, and food handling. Considerable evidence indicates that rats with compromised
DA systems generally also show reduced behavioral
activity and diminished responsiveness to stimuli, and
are highly sensitive to the kinetic requirements of the
task being performed. Thus, in the face of such deficits,
and in the absence of compelling evidence that the major
problem is motivational in nature, attributing the
behavioral effects of high doses of DA antagonists or
striatal DA depletions to a ‘reward’ deficit seems to be
inappropriate.
7.3. Brain DA and learning
A recent trend in the literature has been to emphasize
that DA systems are involved in aspects of learning. In
view of the emphasis of this review on motivational
processes, a thorough review of the learning literature
would be impossible in the present context. Nevertheless, it is useful to discuss briefly a few points that
need to be considered in attempting to integrate this
literature with the rest of the paper. First of all, there
have been a number of studies of the effects of DA
antagonism and DA depletions in various learning
tasks, and the results appear to vary greatly from task
to task. Short term memory and instrumental discrimination processes were not found to be impaired in some
studies [8,12,162,163,202]. Some aspects of S /S associa-
16
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
tive processes may be impaired by DA antagonism,
while others appear to be intact [18,210]. Spatial working memory performance in the radial arm maze was not
disrupted by high doses of haloperidol injected directly
into nucleus accumbens [107], while memory consolidation in a water maze was disrupted by post-trial
infusions of sulpiride into nucleus accumbens [179].
The establishment of place conditioning is affected
consistently by DA antagonists [4,5,53]. DA systems
are involved in the establishment of conditioned reinforcement [14,60,100,225]. Striatal and accumbens DA
systems also are involved in aspects of procedural
learning [178]. Nevertheless, some important points
need to be emphasized in considering this literature in
the context of the present review. Studies indicating that
DA systems are involved in aspects of learning do not
provide support for the notion that DA mediates
motivational aspects of primary reward or positive
reinforcement. Although it is true that reinforcement
involves associative mechanisms, it certainly is not true
that all associative mechanisms can be described as
positive reinforcement. For example, accumbens DA is
known to be activated by stress (see reviews by Gray et
al. [75], and Salamone, [157]), and accumbens DA
depletions severely disrupt lever pressing avoidance
responses [130]. Place aversion, which is a form of
punishment, is impaired by DA antagonists [4,53].
Passive avoidance learning, which again involves punishment, and not reinforcement, also is impaired by
accumbens DA depletions [177]. It should be emphasized that implicating a brain system in some aspect of
learning does not provide evidence that it mediates
motivational aspects of ‘reward’. For example, several
researchers have suggested that accumbens DA may be
involved in aspects of associative conditioning to
appetitive, aversive, and even neutral stimuli
[75,142,144,227]. Thus, it is clearly inaccurate to refer
to these learning studies as providing support for the
DA hypothesis of reinforcement or ‘reward’. Most
importantly for the scope of the present review, it
cannot be said that the learning literature provides any
support for the notion that DA systems mediate primary
appetitive motivation for natural stimuli such as food.
Although DA agonists and antagonists can affect the
process of conditioned reinforcement, according to
Wolterink et al. [225] ‘‘alterations in primary motivation
do not underlie the changes in response to conditioned
reinforcement’’. In reviewing the literature on the
involvement of nucleus accumbens circuitry in learning,
Kelley [102] stated that ‘‘dopamine depletion or antagonism in the accumbens does not affect primary
motivation for food’’.
Another important consideration is that manipulations can alter the behavioral outcomes in learning
experiments by affecting processes other than S /S or S /
R associations. The learning literature is full of examples
of attentional, arousal, or behavioral organization
problems resulting in impaired performance on memory
tasks, either in acquisition or retrieval. Studies of
classical conditioning demonstrated that DA antagonists did not appear to block the formation of S /S
associations directly, but did affect performance by
blunting the conditioned and unconditioned excitatory
properties of stimuli [80]. Considerable evidence indicates that accumbens DA is involved in the sensorimotor gating of the startle response [192]. In short, it is
possible that DA in accumbens is involved in arousal or
attentional processes that affect learning and other
cognitive processes [69,75,85,109,165], but that DA itself
is not necessarily a direct mediator of the formation of
S /S or S /R associations. DA could be acting as a
modulator of input/output relations in the neural
circuitry in accumbens, and different channels of
information could pass through distinct local circuits,
so that some specific pathways amplify behavioral
reactivity to stimuli, while other pathways amplify the
impact of stimuli on cognitive functions.
7.4. Wanting versus liking
One of the most interesting and influential ideas to
emerge from the DA literature in the last few years has
been the notion of ‘incentive-salience’, put forth by
Berridge, Robinson and their colleagues. In a series of
articles [16 /18], they have argued adamantly and
cogently against the notion that DA mediates hedonic
aspects of the response to motivational stimuli. These
authors point to the substantial literature demonstrating
that appetitive taste reactivity to sweet solutions is
unimpaired by DA antagonists, whole forebrain DA
depletions, or by DA depletions specific to nucleus
accumbens [16,18,19,204]. Nevertheless, these authors
also seem to agree with the position offered by Smith
[184] and others that appetite for food is impaired by
interfering with accumbens DA. In order to reconcile
what is seen as a potential discrepancy in the literature,
it is argued by Berridge and Robinson that incentive
motivation is not a unitary phenomenon. Thus, an
important distinction is made between ‘liking’ versus
‘wanting’. According to Berridge and Robinson [18]
‘‘dopamine systems are necessary for ‘wanting’ incentives, but not for ‘liking’ them or for learning new ‘likes’
or ‘dislikes’’’. Behavioral tests that are said to measure
wanting include ‘consumption tests, choice tests, place
preference, instrumental performance’ [18].
In discussing their views, Berridge and Robinson [18]
also provided an thorough review of the literature
involving studies of the effects of DA depletions on
the concurrent lever pressing/chow feeding task and the
T-maze task [42,45,162,163,169], which are discussed
above. In the Berridge and Robinson [18] article, this
discussion was in a section that was intended to review
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
areas of research that apparently do not fit with their
incentive salience model. In fact, there only appears to
be one major source of disagreement between the
position offered by Berridge and Robinson [18] and
that offered in the present work. Berridge and Robinson
[18] appear to be convinced that the fundamental nature
of the impairments produced by DA antagonists and
accumbens DA depletions is somewhere in the realm of
directional aspects of primary incentive motivation, i.e.
the tendency to engage directly in food intake, or the
appetite or ‘attraction’ for food. These authors reviewed
the results of the concurrent lever pressing/feeding
studies (i.e. decreased lever pressing and increased
chow consumption after accumbens DA depletions,
see references [42,45,162,163,169]), but nevertheless
argued that interfering with DA does not necessarily
preserve the original degree of incentive motivation for
food [18]. Yet, a detailed examination of the literature
does not provide evidence for a deficit in ‘attraction’ to
food or consumption of food by the conditions that
induce the shift away from lever pressing or barrier
climbing towards the approach and consumption of
food. For example, 0.1 mg/kg haloperidol caused shifts
in both the operant and T-maze versions of the response
allocation tasks [42,162,163,169]. Yet, this dose of
haloperidol did not alter consumption of pellets or
chow, or preference between pellets or chow, in freefeeding choice tests, nor did it alter preference between a
high versus a low density of food reinforcement when no
barrier was present [162,163,169]. Nucleus accumbens
DA depletions also caused shifts in behavior in operant
and T-maze versions of the response allocation tasks
[43 /45,162,163,169], yet detailed analysis of feeding
behavior showed that rats with accumbens DA depletions did not show impairments in total food intake, rate
of feeding or total time spent feeding [168]. The time
spent feeding is an important measure in view of the
operant literature showing that time allocation is an
important behavioral marker of reinforcement value
(e.g. [13]). Reducing appetite for food by pre-feeding or
by injection of the stimulant and appetite suppressant
amphetamine did not decrease lever pressing and
increase chow consumption, but instead, suppressed
both types of food gathering behavior [42,169]. In
addition, the pattern of effects produced by DA
antagonists and accumbens DA depletions in rats
performing on the concurrent lever pressing/chow feeding task was different from the pattern of effects
produced by the serotonergic appetite suppressant,
fenfluramine [161]. Thus, there is no evidence to indicate
that the specific conditions that alter behavior on the
operant and T-maze response allocation tasks, (e.g. low
doses of DA antagonists, accumbens DA depletions) are
suppressing lever pressing or barrier climbing because of
reduced appetite, or a diminished attraction to food, as
measured by consumption itself. Rather, the evidence
17
from this literature indicates that the instrumental
response requirement is the major factor determining
the shifts in behavior that are observed after DA
antagonism or depletion.
A potential resolution to this apparent difference of
opinion could perhaps be achieved by applying the same
logic to ‘wanting’ that Berridge and Robinson apply to
the general concept of incentive motivation. It has been
argued that reward is not a unitary phenomenon, and
this argument provided the conceptual basis for dissociating this complex process into liking versus wanting
[16,18,19]. Yet, by a similar logic, it can also be argued
that ‘wanting’ is not a unitary phenomenon, and that
this aspect of incentive motivation can be further
divided into components. In other words, while one
could define ‘wanting’ in terms of how much food an
organism consumes if it is directly in front of them,
other aspects of ‘wanting’ include the tendency to
instigate and sustain instrumental actions, and to work
to obtain the food (i.e. effort in the reinforcementseeking behavior). It can be argued that, just as
‘wanting’ can be distinguished from ‘liking’, then wanting as ‘appetite to consume’ can be distinguished from
wanting as ‘working to obtain’ (i.e. tendency to work for
motivational stimulus, and overcome response constraints, activation for engaging in vigorous instrumental actions). Indeed, this distinction is apparent in some
of the language used by Berridge and his colleagues in
attempting to describe ‘wanting’ [17,18] (see Table 3).
Moreover, much of the literature on the effects of
accumbens DA depletions and DA antagonism seems
to offer evidence in favor of the validity of such a
distinction [11,43 /45,162,163,168,169]. Thus, accumbens DA depletions appear to dissociate between
different components of ‘wanting’, impairing some
aspects, while leaving others intact (Fig. 1).
7.5. Behavioral activation, behavioral economics, and the
ergonomics of work requirements in instrumental behavior
It is important for organisms to be able to detect and
consume food if it is immediately available, yet it also is
Table 3
Language that represents distinct components of ‘wanting’ in the
incentive salience literature
Appetite to consume food
‘. . .an object of attraction’
(p. 313; ref. [18])
‘. . .whether an animal will choose it, consume it’
(p. 316, ref. [18])
‘. . .measured by voluntary intake, preference tests’ (p. 317, ref. [18])
Activation to work for food
‘animals will work to acquire. . .’
‘promote motivation to work for a food reward’
‘willingness to obtain a reward’
(p. 313, ref. [18])
(p. 182, ref. [17])
(p. 182, ref. [17])
All of these phrases occur in the cited articles, in the context of
discussing ‘wanting’ for food and other motivational stimuli.
18
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
Fig. 1. According to the incentive salience model, the process of
incentive motivation can be broken down into two components, which
are known as ‘liking’ and ‘wanting’. However, the present review of the
literature indicates that accumbens DA depletions can blunt components of wanting, while leaving others intact. Thus, in the present
review it is suggested that ‘wanting’ can itself be dissociated into
distinct components, and that accumbens DA depletions have a
greater effect upon the expenditure of effort in reinforcement-seeking
behavior, while leaving appetite components basically intact.
critical for organisms to employ instrumental behavior
processes (i.e. food seeking behavior) to procure food
when it is not immediately accessible, even if it requires
considerable time or effort. Instrumental behavior is a
very complex and multi-faceted phenomenon, with
several factors influencing response output (e.g. Pavlovian and instrumental associative factors, motivational
processes, sensorimotor processes, executive function;
[1,20,36,50,61,62,154,155,165]). As noted above, instrumental actions increase the proximity and availability of
motivational stimuli, but in addition they often are
characterized by a high degree of activation, vigor,
effort or persistence in work output. Behavioral activation has been emphasized as a fundamental aspect of
motivation for several decades [34,35,55,81,106,172]. In
some cases, behavioral activation is manifested as broad
or general increases in a variety of behaviors such as
adjunctive behaviors or schedule-induced motor activities [103,104,129,211]. In addition, the behavioral
processes that activate or invigorate animals also
influence instrumental behavior [106,154,156,159], and
this invigoration conveys adaptive advantages because
organisms often are separated from significant stimuli
such as food by environmental constraints or obstacles
(i.e. response or procurement ‘costs’). A wide variety of
investigators who come from different fields such as
psychology and ethology, some of whom study foraging,
while others employ ‘economic’ models of operant
conditioning, have come to the conclusion that workrelated response procurement ‘costs’ exert a profound
effect over instrumental behavior [3,37,38,67,90,91,
98,115 /117,149,188,189]. Behavioral activation can be
seen, in part, as an aspect of motivation that facilitates
the ability of organisms to overcome instrumental
response costs.
As well as being an important part of the behavioral
literature on motivation, the concept of behavioral
activation has had substantial influence over studies of
DA function. For example, scheduled presentation of
food to food deprived animals can result in a high
degree of motor activity [106,129], and this scheduleinduced activity is accompanied by substantial increases
in accumbens DA release [129,211]. Schedule-induced
activity is blunted by systemic DA antagonists [156,159]
and by accumbens DA depletions [129]. Several years
ago, it was suggested that nucleus accumbens acts as an
interface between the limbic system and the motor
system, which facilitates the influence of emotional
and motivational systems on motor output [134]. Several
researchers have emphasized that accumbens DA is
involved in various aspects of behavioral activation
(also known as ‘invigoration’ or ‘specific activation’) [52,62,93,105,111/113,129,130,133,154 /156,158,
159,165]. It has been suggested that accumbens DA
may be particularly important for mediating the activating effects of conditioned stimuli that elicit and sustain
instrumental behavior in the absence of primary reinforcement [154], and several recent studies have
elegantly demonstrated how nucleus accumbens and
related circuitry is involved in Pavlovian processes
related to behavioral activation and the facilitation of
instrumental behavior [61,142,144]. Several studies have
demonstrated that DA antagonists and accumbens DA
depletions reduce response speed [9,41,92,160,
165,168,185]. Moreover, as reviewed above, there is an
enormous body of evidence demonstrating that DA
systems, particularly in nucleus accumbens, are important for enabling animals to overcome the response
procurement costs that separate them from significant
stimuli such as food [42,44,45,93,101,110,123,139,
140,154,155,157,159/163,165,169,170,194].
It is evident that the effects of accumbens DA
depletions interact very powerfully with the task requirements of the instrumental response. Work-related
response procurement costs strongly influence which
schedules or tasks are sensitive to the effects of
accumbens DA depletions. Nevertheless, one should
not assume that caloric expenditure or force requirements, in a literal sense, are the sole factors that make
work more difficult in animals that have compromised
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
DA function. Various forms of work, including schedules of reinforcement, not only have force requirements, but they also have temporal components as well.
Although we can state, with reasonable support, that the
effects of accumbens DA depletions differ depending
upon the work requirements of the task, it is nevertheless true that we don’t fully understand which
particular aspects of effort render some tasks relatively
sensitive to dopaminergic manipulations. Across a
broad range of schedules, the effects of accumbens DA
depletions seem to depend upon baseline response rate,
with higher rate schedules being more greatly sensitive
to the effects of DA depletion [160]. Yet, under other
conditions, the baseline response rate seems to be less
important. For example, if an animal is responding on a
FR300 schedule for 6 reinforcement pellets per ratio,
accumbens DA depletions have a much greater effect
than if a rat is responding on a FR50 schedule for one
pellet [170]. This difference is evident even though the
two schedules produce basically the same rates of
responding under control conditions, and both schedules have the same molar relation between responding
and reinforcement. Clearly, animals with DA depletions
are not merely sensitive to the instrumental response
requirement, but also are sensitive to how the response
requirement is organized [170]. In addition, these data
suggest that temporal factors, such as the delayed or
intermittent nature of reinforcement, can also be important. Rats with accumbens DA depletions appear to
be more dependent upon primary reinforcement, and
are unable to sustain the output of large ratios over long
periods of time in the absence of primary reinforcement
[170]. This observation is consistent with data showing
that dopaminergic drugs or cell body lesions of nucleus
accumbens alter choice based upon different delays of
reinforcement [27,28,209]. Yet, the intermittent nature
of reinforcement alone also cannot explain why performance on some schedules is so greatly impaired by
accumbens DA depletions. For example, the high
sensitivity of the FR64 schedule to DA depletion [1]
cannot be explained simply because of the intermittence
of reinforcement, because interval schedules with similar
molar reinforcement densities are much less affected by
DA depletion (e.g. [185]). In a recent study [41], the
effects of accumbens DA depletions were evaluated
using two different interval schedules. One schedule
was a VI-30 s, and the other was a VI-30 s with an
additional ratio requirement (FR5) attached. Accumbens DA depletion had no effect on VI-30 performance,
but did substantially impair responding on the schedule
that had the ratio requirement added [41]. Thus, despite
the fact that the programmed intermittence of reinforcement was the same in both schedules, and obtained rates
of reinforcement were very similar, only the schedule
with the higher ratio requirement was sensitive to
accumbens DA depletions. It is possible that several
19
factors, including ratio requirements, baseline response
rate, dependence upon conditioned stimuli, organizational constraints and temporal factors jointly determine
the sensitivity of some schedules to the effects of
accumbens DA depletions [41].
8. Conclusions
Researchers who have attempted to identify the
critical characteristics of reinforcing stimuli or reinforcing activities have generally arrived at an emphasis
upon motivational factors. A thorough review of the
behavioral literature indicates that, across several different investigators offering a multitude of theoretical
approaches, motivation is seen by many as being
fundamental to the process of reinforcement. The
reinforcer has been described as a goal, a commodity,
an incentive, or a stimulus that is being approached,
self-administered, attained or preserved. Reinforcers
also have been described as activities that are preferred,
deprived or in some way being regulated. It is evident
that this ‘motivational’ or ‘regulatory’ view of reinforcement has had a profound influence over the hypothesis
that DA directly mediates ‘reward’ or ‘reinforcement’
processes. Indeed, proponents of the DA/reward hypothesis regularly cite motivational theorists and employ their language. Nevertheless, considerable evidence
indicates that low/moderate doses of DA antagonists,
and depletions of DA in nucleus accumbens, can
suppress instrumental responding for food while, at
the same time, these conditions leave fundamental
aspects of reinforcement (i.e. primary or unconditioned
reinforcement; primary motivation; primary incentive
processes) intact. Several complex features of the
literature on dopaminergic involvement in reinforcement were examined above, and it was argued that the
simple assertions that DA mediates ‘reward’ or ‘reinforcement’ for natural stimuli such as food are inaccurate and grossly oversimplified. Based upon this review
of the literature, it appears as though it is no longer
tenable to assert that drugs of abuse are simply turning
on the brain’s natural ‘reward system’. In relation to the
hypothesis that DA systems are involved in ‘wanting’,
but not ‘liking’, it is suggested in the present review that
‘wanting’ has directional aspects (e.g. appetite to consume food) as well as activational aspects (e.g. tendency
to instigate instrumental behavior; working to obtain
food). Thus, low doses of DA antagonists and accumbens DA depletions do not impair the appetite to
consume food, but are seen as disrupting the tendency
to work for food. According to behavioral economic
principles, DA could be involved in the elasticity of
demand for food in terms of the tendency to pay workrelated response costs. This view is consistent with the
literature showing that low doses of DA antagonists and
20
J.D. Salamone, M. Correa / Behavioural Brain Research 137 (2002) 3 /25
accumbens DA depletions alter the relative allocation of
instrumental responses, making the animals less likely to
engage in instrumental responses that have a high degree
of work-related response costs ([1,160,161,170], see
review in [165]). The effects of accumbens DA depletions
on instrumental lever pressing are highly scheduledependent, and ratio schedules in particular are very
sensitive to the effects of accumbens DA depletions
[1,41,170]. Overall, it appears as though accumbens DA
is important for maintaining effort in instrumental
responding over time in the absence of primary reinforcement [41,170]. Future research must focus upon how
specific aspects of task requirements (i.e. ratio requirements, task difficulty, intermittence of reinforcement,
temporal features of response requirements, dependence
upon conditioned stimuli) interact with the effects of
accumbens DA depletions, and which particular factors
determine the sensitivity of some tasks to the effects of
DA antagonism or depletion.
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
Acknowledgements
Much of the research by John D. Salamone cited in
this manuscript was supported by grants from the
National Science Foundation. Many thanks to Keri
Nowend, Brian Carlson, Jennifer Trevitt, Susana Mingote and Suzanne Weber for their helpful comments.
[18]
[19]
[20]
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