Download Is susceptibility to weight gain characterized by homeostatic or

Physiology & Behavior 82 (2004) 21 – 25
Is susceptibility to weight gain characterized by homeostatic
or hedonic risk factors for overconsumption?
John E. Blundell*, Graham Finlayson
Psychobiology Group, School of Psychology, University of Leeds, Leeds LS2 9JT, UK
Received 1 March 2004; accepted 2 April 2004
Abstract
In any particular group of people—living in the same culture—some gain weight whilst others do not. Overconsumption of food is one
factor contributing to this susceptibility to weight gain. Because all individuals are exposed to a similar range of environmental appetitestimulating factors, the variability in overconsumption must be due to variability in intrinsic psychobiological processes. Such variability is
an inevitable feature of living organisms. This essay explores whether susceptibility to weight gain is caused by variation in homeostatic
processes—such as weak satiety responses to fat, or by hedonic processes—such as hyperresponsivity to the sensory properties of food. The
question also arises whether the homeostatic or hedonic processes function separately and independently, or whether they interact. The
answer to these questions can throw light upon the organization of behaviours associated with weight control, and can help to develop
strategies to prevent weight gain. The theme of this essay was inspired by Gerry Smith’s conceptual and experimental work on both
homeostatic and hedonic mechanisms implicated in the control of food intake.
D 2004 Elsevier Inc. All rights reserved.
Keywords: Overconsumption; Weight gain; Hedonic response
1. Susceptibility to weight gain
Susceptibility to weight gain is associated with metabolic
[1] and behavioural [2] risk factors. Considering metabolic
factors, the tendency to gain weight is associated with a low
basal metabolic rate, low energy cost of physical activity, a
low capacity for fat oxidation, high insulin sensitivity, low
sympathetic nervous system activity, and a low plasma
leptin concentration. However, when a steady state of
obesity occurs, many of these predictors of weight gain
are reversed. Behavioural risk factors can exist for energy
intake (EI) and energy expenditure (EE) and both can lead
to positive energy balance. However, whereas for EE
behaviour (physical activity) can account for between 40%
and 60% of total EE (depending on the amount of volitional
activity, exercise, etc.), behaviour accounts for 100% of EI.
Because changes in EI can be of greater magnitude than in
EE (on a daily basis), it can be argued that behavioural
aspects of EI (i.e., appetite control) constitute risk factors of
greater magnitude than those for EE.
* Corresponding author. Tel.: +44-113-343-5742; fax: +44-113-3436674.
E-mail address: [email protected] (J.E. Blundell).
0031-9384/$ – see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.physbeh.2004.04.021
The behavioural risk factors may be patterns of eating
behaviour, hedonic events which guide and reinforce behaviour, the strength of hunger and satiety sensations, or
preferences for and selection of particular types of foods.
These behavioural risk factors can be regarded as biological
dispositions which create a vulnerability for weight gain and
which manifest themselves through behavioural acts, or
through physiological processes which promote or permit
changes in behaviour. It is an important scientific issue
whether these behavioural risk factors operate independently of each other or interact.
2. Hedonic response: a risk factor for weight gain?
A reasonable proposal is that an exaggerated hedonic
response to the sensory features of foods constitutes a
behavioural risk factor that could promote excessive EI.
Although sedentariness is widespread, there is evidence that
weight-gaining individuals do indeed consume excessive
amounts of food [3] and that weight gain is associated with
specific food habits, including the consumption of fatty
foods, eating outside the home, and the accessibility of
fast/junk foods, each of which is likely to be related to
22
J.E. Blundell, G. Finlayson / Physiology & Behavior 82 (2004) 21–25
enhanced palatability of foods. Physiological satiety signals
can be overwhelmed by the potency of high energy-dense,
highly palatable foods [4] and strong preferences for these
foods are expressed as behavioural traits that constitute risk
factors (e.g., Ref. [5]).
Interestingly, the hedonic response, noted here as a risk
factor, can be viewed differently.
As noted in the recent National Nutrition—Health
Programme (2001 –2005) in France, an individual’s food
choice is a ‘free act’ and eating is recognised as a moment of
pure pleasure. Is it therefore necessary to ‘sacrifice the
gentle principle of pleasure to the all-powerful precautionary principle?’ Consequently, the hedonic response is both a
fundamental aspect of culinary traditions and eating habits,
but also a risk factor for overconsumption. Is it possible to
satisfy the first whilst preventing the second?
3. Homeostasis and hedonics: separate identities?
In the homeostatic approach to energy balance, drives
(such as hunger) that arise in part from biological needs are
balanced by physiological satiety signalling systems. The
substrate comprises a network of neuropeptides and biogenic aminergic neurotransmitters which links peripheral and
central components. This system has been well characterised (e.g., Ref. [6]) and involves insulin, leptin, NPY, AgRP,
MSH, CART, GLP-1, orexins, ghrelins, PYY, and other
peptides along with serotonin pathways and other aminergic
systems. A biological substrate mediating the hedonic
processes surrounding consumption is also being characterised and ostensibly involves glutamate, opioids, benzodiazepines, endocannabinoids, and dopamine pathways (e.g.,
Refs. [7,8]). The circuits for energy homeostasis and hedonic mediation correspond closely to the hypothesised
neural systems involved in food reward, reflecting the
psychological or functional components of ‘wanting’ and
‘liking’ [9]. If homeostatic and hedonic processes are indeed
associated with distinct neural substrates, the extent to
which they operate independently can be investigated.
Researchers have recently attempted to test the independence of the two systems by methodologically separating
hedonic response from appetitive drive. For example, hedonic reactivity measured by subjective ratings and behavioural observation was dissociated from the incentive value
of food by manipulating hunger state and measuring the
reinforcing value of foods using a slot-machine-like progressive ratio computer task [10]. Moreover, a high-palatability food (chocolate) was reduced in rated pleasantness
over 22 successive days of intake, despite the volitional
quantity consumed remaining stable [11].
Pharmacological evidence also suggests that the processes operate independently. For example, in obese participants, administration of the serotonin drug D-fenfluramine
[12] suppressed the sensation of hunger but had no effect on
the appreciation of the pleasantness of food. Conversely,
nalmafene, an opioid agonist, reduced the rated pleasantness
of palatable foods but had no effect on hunger [13].
This double-dissociation concept indicates that appreciation of palatability is associated with a specific substrate
that can be pharmacologically, and to an extent, methodologically dissected from the substrate-mediating hunger
[14]. However, it is still possible for a functional interaction
to occur when the manipulation is made through the natural
commodity (selected food) rather than through a more
selective artificial manipulation (such as a drug).
4. Hunger and pleasure—do they interact?
Considering that most studies have repeatedly shown that
palatability has a positive effect on intake and meal size, this
would suggest that the palatability of foods is involved in
the process of satiation. However, it is less clear whether the
palatability of food also has an influence on feelings of
hunger and satiety [15]. The possibility of an interaction
between palatability and hunger was specifically investigated almost 20 years ago. On separate occasions, participants
consumed a fixed energy meal composed of either highly
preferred foods or less preferred equivalent food items [16].
There was an enhancing effect of palatability (even the sight
of a preferred food) on subsequent hunger which remained
high during the meal. However, this fixed meal design did
not allow the disclosure of any effect on EI. More recently,
an overall increase in hunger following consumption of a
palatable preload and an equivalent decrease in hunger
following a bland preload with corresponding adjustments
in ad libitum intake were revealed [17]. The authors
reported this difference to occur irrespective of preload
energy or macronutrient content.
Using repeated ratings of appetite within a meal whilst
food intake is being constantly monitored, Martin Yeomans
has produced a series of experiments that examined the
interaction of hedonic response to food with hunger. Participants were presented with meals manipulated at three levels
of palatability and showed differential effects of hedonic
response on hunger ratings during ingestion. For the
‘strong’ flavoured test meal, rated hunger decreased monotonically with food consumed. For the ‘bland’ flavoured test
meal, hunger was found to decrease at a slower rate
compared to the strong meal, but increase with intake. In
contrast to these conditions, the optimally flavoured ‘palatable’ test meal was associated with an initial short-lasting
increase in hunger followed by the slowest decrease of all
the conditions. Similar trends were observed by Yeomans et
al. [18] using two levels of palatability.
Several researchers have examined the effect of food
palatability on subsequent satiety. Foods eliciting an enhanced hedonic response appear to promote a more rapid
recovery in hunger up to 3 h following consumption
compared to a less palatable preload [19]. Moreover, there
is evidence that some stimulation of intake occurs over the
J.E. Blundell, G. Finlayson / Physiology & Behavior 82 (2004) 21–25
24-h period following consumption of optimal preference
sweetened yoghurt preloads [20,21]. In a more recent study,
the effect of food palatability on the degree of energy
compensation following preloads has been investigated
[17]. The capacity of people to demonstrate compensation
is usually regarded as a sign of the sensitivity of the system
and indicates good appetite control. However, the presence
of a more palatable food prevented compensation.
In one of the first free-living studies to examine palatability and intake responses, the extent to which hunger was
an intermediary between palatability and meal size was
assessed [22]. Comparing hunger with palatability in a
two-factor multiple regression, the largest reduction in the
palatability b coefficient occurred when it was paired with
before meal hunger rating, suggesting that a portion of the
effect of palatability on intake is mediated through hunger.
Taken together these studies indicate that the response to the
palatability of food does indeed exert an effect on EI, and
this appears to be mediated via a modulation of hunger. This
means that when the homeostatic and hedonic systems are
stimulated simultaneously (by food), a synergy occurs that
modulates the control of appetite. This process appears to
constitute one way through which the hedonic potential of
foods could lead to weight gain.
However, the system does appear to operate asymmetrically; although enhanced hedonic response to foods can
augment hunger (and therefore, food intake), the presence
of strong satiety (developing over the course of a meal) does
not down-regulate palatability (e.g., Ref. [23]). Indeed, it has
been documented that participants in a state of satiety can be
induced to prolong their eating by offering highly palatable
foods [24]. It is also noticeable that the reasons people give
for stopping eating emphasise fullness and loss of hunger
rather than a decline in the pleasantness of the food [25,26].
In other words, participants do not generally perceive
pleasantness to be the most important factor in terminating
meals. However, this may only hold for foods in which the
hedonic value is above some minimum threshold [27].
5. Food choice, hedonic response, and obesity
In addition to an interaction between palatability and
hunger, the perceived pleasantness or hedonic response to
foods could also modulate appetite control indirectly by
influencing the choice of foods. There is considerable
evidence that this is the case. In an experiment in which
participants sampled a range of foods containing varying
amounts of fat and rated their sensory preferences, there was
a positive relationship between the rated pleasantness of the
fat content of the foods and measures of the adiposity of the
participants [28]. The fatter the participant, the greater was
his/her rated pleasantness of the fatty foods. More recently,
the food choices of monozygotic twins discordant for body
weight have been assessed [29]. The twins with the highest
degree of fatness displayed a significantly higher preference
23
for fatty foods. If it is assumed that the expression of food
preferences is influenced at least in part by the pleasure
yielded by the foods, then these studies have demonstrated
that levels of body fat are associated with greater rating of
pleasantness of fat-containing foods.
It should be noted that food palatability can also affect
the reward value of food during ingestion. The phenomenon
called ‘sensory-specific satiety’ describes the habituation of
specific sensory neurons in response to the prolonged
application of the same, but not a novel stimulus [30].
Sensory-specific satiety is shown by a reduction in hedonics
of a food being consumed, with little change in hedonics of
foods not consumed [31]. From this, it has been argued that
being given the opportunity to consume novel foods in a
meal can result in a greater intake than if participants are
offered more of the same food they have recently consumed
[32]. Alternatively, it has been proposed [14,33] that the
initial exposure to sensory characteristics of a new food
should be viewed as a method to stimulate eating (e.g.,
sensitization) rather than being an important factor of
satiation. Consequently, exposure to new foods can augment
food consumption during a meal rather than the pleasantness
of foods decreasing due to prior consumption [14].
However, the contradiction of stimulating and inhibiting
effects of exposure to the sensory properties of food on
eating can be integrated in that the sensory properties of food
may provide positive and negative feedback for eating
through orosensory stimulation of the preabsorptive receptors along the gastrointestinal tract that are sensitive to the
chemical, colligative, or mechanical stimuli of food [34].
Therefore, as eating ensues, positive feedback dominates the
system, causing consumption to increase. As more stimulation occurs, negative feedback increases in strength, until the
potencies of the positive and negative feedbacks are equal,
causing consumption to decrease. This supports the idea that
sensory (and hedonic) properties of food are important for
the promotion and inhibition of eating. It could be that the
sheer variety of highly palatable foods available to an
individual during any one meal may increase the amount
of time required to balance the positive and negative feedbacks, causing a longer, and larger, eating bout [34].
Recent research has explored the link between vulnerability for addiction and its relation to brain dopamine
activity and potential excessive weight gain. Sensitivity to
reward (STR), a psychobiological trait reportedly linked to
the neurobiology of the mesolimbic dopamine pathway, was
used to examine how (an)hedonia, the capacity to experience pleasure, might relate to overconsumption and subsequent weight gain [35]. Contrary to predictions of a linear
relationship between BMI and STR, an inverted U relationship was revealed with overweight participants (BMI >
25 < 30) scoring higher than obese and normal-weight
participants. Is it possible that low anhedonia (high STR)
promotes a life style of hedonically driven overconsumption, which, over time, down-regulates mesolimbic dopamine availability to compensate for its overstimulation? In
24
J.E. Blundell, G. Finlayson / Physiology & Behavior 82 (2004) 21–25
other words, high hedonic responsiveness would be a risk
factor for weight gain (the achievement of obesity) but
would not necessarily characterise an obese person.
There is evidence to support this proposition. For example, PET scans of normal-weight healthy participants eating
a favourite meal revealed an increase in dopamine release
that correlated with the degree of experienced pleasure.
Another study demonstrated that the availability of the
dopamine D2 receptor was decreased in obese participants
in proportion to their BMI [36].
These studies map onto the idea that there is an optimal
level or inverted U relationship between hedonic predisposition and dopamine activation [37]. Participants administered the dopamine agonist methylphenidate found it either
pleasant or unpleasant depending on their DRD2 receptor
levels. Those participants reporting pleasant effects had
significantly lower levels of the dopamine receptor than
those who found it unpleasant [37]. It can therefore be
construed that potent stimuli (including palatable foods) elicit
a positive hedonic response through the stimulation of
dopamine activity in people of an anhedonic predisposition.
However, there is no evidence to date that tests the notion that
particularly hedonic individuals respond aversively to highly
palatable foods. It has been suggested that dopamine activity
relating to excessive food consumption might only involve
activation of brain reward circuitry within normal limits, with
other psychological factors exerting stronger effects [38].
Recent investigations of behavioural phenotypes characterised by habitual food choices suggests that the hedonic
response to palatable food can influence appetite control via
effects on both food choice and EI. Groups of overweight
and lean young males matched for age and the habitual high
consumption of fat (high-fat phenotypes) were compared
[39]. Although both groups were eating a diet known to
favour a positive energy balance, the overweight phenotypes
consumed greater amounts of the high-fat foods in a test
meal and reported greater feelings of pleasantness, satisfaction, and tastiness for the foods consumed. One interpretation of these data is that, for at least this group of overweight
people (susceptible to weight gain), they habitually selfselect (fatty/palatable) foods with a high probability of
generating a positive energy balance (on the basis of their
energy density), consume these foods in greater amounts,
and derive greater pleasure from this eating. This outcome
also demonstrates that certain high-fat phenotypes—susceptible to weight gain—have a disposition to perceive foods as
being more pleasant than their lean counterparts (who
consume the same habitual high-fat diet). Given this capacity to obtain a high level of pleasure from foods (and
eating), it is not surprising that obese people show a
tendency to self-select high-palatability foods. It is yet to
be determined whether this indicates a supersensitivity in
components of the neural circuitry forming the substrate for
hedonic properties of foods or whether it reflects a more
global sensitivity in the ability to experience pleasure from
natural reinforcers in the environment.
6. Pharmaceutical strategies
Although low levels of physical activity contribute to
excess weight gain, there is no doubt that many weightgaining and obese individuals display behavioural risk
factors expressed as patterns of eating, food selection, weak
satiety, and a recurring drive to eat that favour the attainment of a positive energy balance [2]. To these risk factors,
enhanced hedonic capacity should be added. Currently
pharmaceutical strategies for the treatment of obesity are
concerned with the reduction of energy assimilated—by
improving satiety (sibutramine) or by reducing fat intake
and fat digestion (Orlistat). Given the evidence cited above,
some consideration should be given to the concept of
controlling the hedonic response to foods, particularly in
the light of the increasing palatability of foods entering the
market place. The strategy would nullify one significant risk
factor that predisposes people to weight gain via a number
of means. The identification of a neural substrate that
mediates aspects of the hedonic response or reward value
of foods, identifies pharmacological targets. Of particular
interest are the endocannabinoids which are known to be
involved in food consumption and especially the intake of
highly palatable foods [40]. It can be noted that the action of
endocannabinoids may be via incentive motivational properties of food stimuli as well as via effects on reward
processes [41]. These mechanisms have implications for
the way in which endocannabinoid activity could modify
the pattern of eating and profile of food choices in humans.
Interestingly, CB1 receptor antagonists, such as SR141716A
(Rimonabant), may be effective in helping people to diminish consumption of high-risk foods and adapt to more
appropriate food choices and resist cravings. This type of
approach would add a useful dimension to pharmaceutical
treatments and may be especially helpful for a subset of
weight-gaining and obese people who overconsume because
of a potent hedonic response to food. It should also be noted
in passing that the endocannabinoids may also be involved
in the homeostatic control of appetite [42]. Because of the
distribution of CB1 receptors in the brain and periphery, an
‘endocannabinoid bridge’ could function as a link between
homeostatic and hedonic processes controlling patterns of
eating. We conclude that overconsumption and weight gain
can be brought about by either homeostatic or hedonic risk
factors, and that such risk factors can be colocalized in
certain susceptible individuals, and subserved by overlapping neural circuits.
7. Postscript
The senior author (JB) gratefully acknowledges the
career-long influence of G.P. (Gerry) Smith on his philosophical approach to scientific work and on the methodology through which ideas have been implemented.
Especially important has been the example set by Gerry
J.E. Blundell, G. Finlayson / Physiology & Behavior 82 (2004) 21–25
for the precision and clarity of conceptual issues and the
insistence on rigour and accuracy in experimentation. Because science advances through the transmission of good
ideas and strong methodology, it is intended that the
inspiration of Gerry Smith will be inherited by GF. At
another level, JB’s daughter, Joanna (3 years old at the
time), still has fond memories of being taken by Gerry on a
reverential visit to Sherrington’s laboratory in the Physiology Department of the University of Liverpool (1986). A
fascination for science can be transmitted in diverse ways.
Acknowledgements
Funded by the European Commission, Quality of Life
and Management of Living Resources, QLK1-CT-200000515.
References
[1] Gautier JF, Ravussin E. Diabetes and obesity among the Pima Indians.
M S-Med Sci 2000;16:1057 – 62.
[2] Blundell JE, Cooling J. Routes to obesity: phenotypes, food choices
and activity. Br J Nutr 2000;20:S33 – 8.
[3] Pearcey SM, de Castro JM. Food intake and meal patterns of weightstable and weight-gaining persons. Am J Clin Nutr 2002;76:107 – 12.
[4] Blundell JE, Lawton C, Cotton JR, Macdiarmid JI. Control of human
appetite: implications for the intake of dietary fat. Annu Rev Nutr
1996;16:285 – 319.
[5] Blundell JE. Food choice phenotypes: biology or environment: biology or environment. Eur J Clin Nutr 2001;54(Suppl. 4):S4 – 5.
[6] Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central
nervous system control of food intake. Nature 2000;404:661 – 71.
[7] Saper CB, Chou CT, Elemquist JK. The need to feed: homeostatic and
hedonic control of eating. Neuron 2002;36:199 – 211.
[8] Flier JS. Obesity wars: molecular progress confronts and expanding
epidemic. Cell 2004;116:337 – 50.
[9] Berridge KC. Food reward: brain substrates of wanting and liking.
Neurosci Biobehav Rev 1996;20:1 – 25.
[10] Epstein LH, Truesdale R, Wojcik A, Paluch RA, Raynor HA. Effects
of deprivation on hedonics and reinforcing value of food. Physiol
Behav 2003;78:221 – 7.
[11] Hetherington MM, Pirie LM, Nabb S. Stimulus satiation: effects of
repeated exposure to foods on pleasantness and intake. Appetite
2002;38:19 – 28.
[12] Blundell JE, Hill AJ. Serotoninergic modulation of the pattern of
eating and the profile of hunger-satiety in humans. Int J Obes
1987;11:141 – 53.
[13] Yeomans MR, Wright P. Lower pleasantness of palatable foods in
nalmafene-treated human volunteers. Appetite 1991;16:249 – 59.
[14] Blundell JE, Rogers PJ. Hunger, hedonics, and the control of satiation
and satiety. In: Friedman MI, Tordoff MG, Kare MR, editors. Chemical Senses, Appetite and Nutrition, vol. 4. New York: Marcel Dekker;
1991. p. 127 – 48.
[15] de Graaf C, de Jong LS, Lambers AC. Palatability affects satiation but
not satiety. Physiol Behav 1999;66:681 – 8.
[16] Hill AJ, Magson LD, Blundell JE. Hunger and palatability: tracking
ratings of subjective experience before, during and after the consumption of preferred and less preferred food. Appetite 1984;5:361 – 71.
[17] Yeomans MR, Lee MD, Gray RW, French SJ. Effects of test-meal
palatability on compensatory eating following disguised fat and carbohydrate preloads. Int J Obes 2001;25:1215 – 24.
25
[18] Yeomans MR, Gray RW, Mitchell CJ, True S. Independent effects of
palatability and within-meal pauses on intake and appetite ratings in
human volunteers. Appetite 1997;29:61 – 76.
[19] Rogers PJ, Blundell JE. Umami and appetite: effects of monosodium
glutamate on hunger and food intake in human subjects. Physiol
Behav 1990;48:801 – 4.
[20] Monneuse MO, Bellisle F, Louis-Sylverstre J. Responses to an intense
sweetener in humans: immediate preference and delayed effects on
intake. Physiol Behav 1991;49:325 – 30.
[21] Perez C, Dalix AM, Guy-Grand B, Bellisle F. Human responses to
five concentrations of sucrose in a dairy product: Immediate and
delayed palatability effects. Appetite 1994;23:165 – 78.
[22] de Castro JM, Bellisle F, Dalix AM, Pearcey SM. Palatability and
intake relationships in free-living humans: characterization and independence of influence in North Americans. Physiol Behav 2000;
70:343 – 50.
[23] Yeomans MR, Symes T. Individual differences in the use of pleasantness and palatability ratings. Appetite 1999;32:383 – 94.
[24] Looy H, Callaghan S, Weingarten HP. Hedonic response of sucrose
likers and dislikers to other gustatory stimuli. Physiol Behav 1992;52:
219 – 25.
[25] Mook DG, Votaw MC. How important is hedonism? Reasons given
by college students for ending a meal. Appetite 1992;18:69 – 75.
[26] Zandstra EH, de Graaf C, Mela DJ, Van Staveren WA. Short- and
long-term effects of changes in pleasantness on food intake. Appetite
2000;34:253 – 60.
[27] Guy-Grand B, Lehnert V, Doassans M, Bellisle F. Type of test-meal
affects palatability and eating style in humans. Appetite 1994;22:
125 – 34.
[28] Mela DJ, Sacchetti DA. Sensory preferences for fats: relationship with
diet and body composition. Am J Clin Nutr 1991;53:908 – 15.
[29] Rissanen A, Hakala P, Lissner L, Mattlar CE, Koskenvuo M, Ronnemaa T. Acquired preference especially for dietary fat and obesity: a
study of weight-discordant monozygotic twin pairs. Int J Obes
2002;26:973 – 7.
[30] Rolls ET. Taste and olfactory processing in the brain and its relation to
the control of eating. Crit Rev Neurobiol 1997;11:263 – 87.
[31] Sclafani A. The hedonics of sugar and starch. In: Bolles RC, editor.
The hedonics of taste. Hillsdale (NJ): Erlbaum; 1991. p. 59 – 87.
[32] Rolls ET. Central nervous mechanisms related to feeding and appetite.
Brit Med Bull 1981;37:131 – 4.
[33] Mela DJ, Rogers PJ. Food, eating and obesity: the psychobiological
basis of appetite and weight control. London: Chapman & Hall,
1998.
[34] Smith GP. The direct and indirect controls of meal size. Neurosci
Biobehav Rev 1996;20:41 – 5.
[35] Davis C, Strachan S, Berkson M. Sensitivity to reward: implications
for overeating and overweight. Appetite.: In press.
[36] Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, et al.
Brain dopamine and obesity. Lancet 2001;357:354 – 7.
[37] Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Gifford A, et
al. Prediction of reinforcing responses to psychostimulants in humans
by brain dopamine D2 receptor levels. Am J Psychiatr 1999;156:
1440 – 3.
[38] Robinson TE, Berridge KC. Addict Annu Rev Psychol 2003;54:
25 – 53.
[39] Le Noury J, Lawton CL, Blundell JE. Food choice and hedonic
responses: difference between overweight and lean high fat phenotypes. Int J Obes 2002;26:S125.
[40] Kirkham TC, Williams CM. Synergistic effects of opioid and cannabinoid antagonists on food intake. Psychopharmacology 2001;153:
267 – 70.
[41] Kirkham TC, Williams CM. Endogenous cannabinoids and appetite.
Nutr Res Rev 2001;14:65 – 86.
[42] Harrold JA, Williams G. The cannabinoid system: a role in both the
homeostatic and hedonic control of eating? Br J Nutr 2003;90:
729 – 34.