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Common Features of Addiction
Physical versus Psychological Addiction
Tolerance:
The fact that increasingly large doses of drugs must be taken to
achieve a particular effect; caused by compensatory mechanisms
that oppose the effect of the drug.
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Common Features of Addiction
Physical versus Psychological Addiction
Withdrawal symptoms:
The appearance of symptoms opposite to those produced by a drug
when the drug is suddenly no longer taken; caused by the presence
of compensatory mechanisms.
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Common Features of Addiction
Positive Reinforcement
Positive reinforcement:
Addictive drugs have reinforcing effects. That is, their effects include
activation of the reinforcement mechanism.
This activation strengthens the response that was just made, namely,
taking the drug.
Drugs with the most immediate effects tend to be the most addictive.
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Common Features of Addiction
Negative reinforcement
Negative reinforcement:
The removal or reduction of an aversive stimulus that is contingent on a
particular response, with an attendant increase in the frequency of
that response.
If taking a drug “turns off” aversive withdrawal effects it is a negatively
reinforced behavior that will increase in frequency.
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Common Features of Addiction
Craving and Relapse
Craving:
The desire to take a drug.
Relapse:
A return to the use of a drug following a period of abstinence from use
of the drug.
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Common Features of Addiction
Craving and Relapse
Reinstatement model:
An animal is trained to make a response that is reinforced by in
intravenous injection of a drug.
Next, the response is extinguished by providing injections of a saline
solution.
Once responding has extinguished, the animal is given a free injection
of the drug.
In response to the drug, the animal begins responding once again.
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Common Features of Addiction
Craving and Relapse
Brain mechanisms:
Relapse appears to involve activation of the mesolimbic system of
dopaminergic neurons.
Relapse caused by stimuli previously associated with cocaine appears
to involve the amygdala as well as the mesolimbic dopamine system
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Common Features of Addiction
Craving and Relapse
Brain mechanisms:
PET scan studies have demonstrated activity of the prefrontal cortex
and the anterior cingulate cortex of cocaine abusers was less active
than that of normal subjects during abstinence.
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Common Features of Addiction
Craving and Relapse
Stress:
Clinicians have long observed that stressful situations can cause a
former drug addict to relapse.
Stressful stimuli, even those that occur early in life, increase an
animal’s susceptibility to drug addiction.
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Common Features of Addiction
Craving and Relapse
Stress:
Stress is associated with the release of CRH in the brain by cells of the
central nucleus of the amygdala whose terminals release this peptide
in the bed nucleus of the stria terminalis.
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Commonly Abused Drugs
Opiates
Cocaine and Amphetamines
Nicotine
Alcohol and Barbiturates
Cannabis
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Common Features of Addiction
Opiates:
Endogenous opiates are secreted when an animal is performing
behaviors that are important to its survival such as fighting with
another animal.
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Common Features of Addiction
Opiates:
Endogenously released opioids stimulate receptors that produce
analgesia that reduces the inhibitory effects of pain and positive
reinforcement that encourages the animal to continue with what is
was doing.
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Common Features of Addiction
Opiates:
Opium is derived from a sticky resin produced by the opium poppy and
has been eaten or smoked for centuries.
Heroin is the most commonly abused opiate.
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Common Features of Addiction
Neural Basis of Reinforcing Effects
Opiate Administration:
When an opiate is administered it stimulates opiate receptors located
on neurons in various parts of the brain and cause a variety of effects
including:
Analgesia
Hypothermia
Sedation
Reinforcement
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Common Features of Addiction
Neural Basis of Reinforcing Effects
Dynorphin:
An endogenous opioid; the natural ligand for
k-opiate receptors.
Conditioned place preference:
The learned preference for a location in which an organism
encountered a reinforcing stimulus, such as food or a reinforcing
drug.
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Common Features of Addiction
Neural Basis of Reinforcing Effects
Naloxone:
A drug that blocks mu opiate receptors; antagonizes the reinforcing and
sedative effects of opiates.
Pimozide:
A drug that blocks dopamine receptors.
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Common Features of Addiction
Neural Basis of Withdrawal Effects
Brain mechanisms:
Several regions of the brain have been implicated in withdrawal effects
including the periaqueductal gray matter, the locus coeruleus, and the
amygdala.
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Common Features of Addiction
Cocaine and Amphetamine
Cocaine and amphetamine have similar behavioral effects, because
both act as potent dopamine agonists.
The site of action of cocaine and amphetamine are different.
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Common Features of Addiction
Cocaine and Amphetamine
Cocaine:
Cocaine binds with and deactivates the dopamine transporter proteins,
thus blocking the reuptake of dopamine after it is released by terminal
buttons, thus acting as a dopamine agonist.
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Common Features of Addiction
Cannabis
Brain mechanisms:
THC administration stimulates release of dopamine in the nucleus
accumbens and the ventral tegmental area
The drug appears to act directly on dopaminergic terminal buttonspresumably on presynaptic heteroreceptors.
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Common Features of Addiction
Cocaine and Amphetamine
Amphetamine:
Amphetamine inhibits the reuptake of dopamine, but its most important
effects is to directly stimulate the release of dopamine from terminal
buttons.
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Common Features of Addiction
Cocaine and Amphetamine
Effect of cocaine and amphetamine:
The effects of cocaine and amphetamine seen in people who abuse
these drugs regularly include psychotic behavior: hallucinations,
delusions of persecution (paranoid behavior), mood disturbances,
and repetitive motor behaviors.
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Common Features of Addiction
Cocaine and Amphetamine
Effect of cocaine and amphetamine:
Prior abusers of methamphetamine showed a decrease in the number
of dopamine transporters in the caudate nucleus and putamen,
despite a three year abstinence from the drug.
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Common Features of Addiction
Cocaine and Amphetamine
Effect of cocaine and amphetamine:
Both drugs are potent dopamine agonists, these drugs activate the
mesolimbic system and reinforce drug-taking behavior.
Both drugs increase the concentration of dopamine in the nucleus
accumbens that is a critical site in the reinforcing effect of the drugs.
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Common Features of Addiction
Cocaine and Amphetamine
Effect of cocaine and amphetamine:
Long-term cocaine or amphetamine use does not produce tolerance
and is even likely to produce sensitization to the effects of the drug.
Withdrawal from cocaine does not cause physical symptoms, but it
does cause unpleasant feelings, including dysphoria and decreased
ability to feel pleasure.
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Common Features of Addiction
Nicotine
Nicotine:
Nicotine is an addictive drug and it accounts for more deaths than the
so-called “hard drugs”.
The World Health Organization reported that one-third of the adult
population of the world smokes.
Investigators estimate that by the year 2020, tobacco will be the largest
single health problem worldwide, with 8.4 million deaths per year.
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Common Features of Addiction
Nicotine
Nicotine:
Forty percent of people continue to smoke after having had a
laryngectomy (which is usually performed to treat throat cancer).
More than 50 percent of heart attack survivors continue to smoke, and
about 50 percent of people continue to smoke after submitting to
surgery for lung cancer.
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Common Features of Addiction
Nicotine
Nicotine:
Nicotine stimulates acetylcholine receptors and increases the activity of
dopaminergic neurons of the mesolimbic system, which contain these
receptors, and caused dopamine to be released in the nucleus
accumbens.
Injections of a nicotine agonist into the ventral tegmental area will
reinforce a conditioned place preference.
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Common Features of Addiction
Alcohol and Barbiturates
Alcohol:
Alcohol has greater costs to society than any other drug.
A large percentage of deaths and injuries caused by motor vehicle
accidents are related to alcohol.
The leading cause of mental retardation in the Western world today is
alcohol consumption by pregnant women.
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Common Features of Addiction
Alcohol and Barbiturates
Sites of action:
Alcohol has two primary sites of actions. It serves as an indirect agonist
at GABAA receptors and as an indirect antagonist at NMDA receptors.
Stimulation of both receptors systems triggers apoptosis (cellular
death).
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Common Features of Addiction
Alcohol and Barbiturates
Behavioral effects:
At low doses alcohol produces mild euphoria and has an anxiolytic
effect (reduces anxiety).
At higher doses alcohol produces uncoordination and sedation.
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Common Features of Addiction
Alcohol and Barbiturates
Behavioral effects:
The mild euphoria of alcohol provides positive reinforcement for
continued drinking.
Alcohol also relieves anxiety and continued use is negatively
reinforced.
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Common Features of Addiction
Alcohol and Barbiturates
Brain mechanisms:
Alcohol, like other addictive drugs, increases the activity of the
dopaminergic neurons of the mesolimbic system and increases the
release of dopamine in the nucleus accumbens.
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Common Features of Addiction
Alcohol and Barbiturates
Brain mechanisms:
Alcohol enhances the action of GABA and GABAA receptors and
interferes with the transmission of glutamate at NMDA receptors.
The perceptual effects of alcohol are mimicked by both GABA agonists
and NMDA antagonists.
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Common Features of Addiction
Alcohol and Barbiturates
Brain mechanisms:
Observations strongly suggest that NMDA receptors are responsible for
the seizures produced by alcohol withdrawal.
The sedative effect of alcohol also appears to exerted at the GABAA
receptor.
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Common Features of Addiction
Cannabis
Cannabis:
THC is the active ingredient in marijuana.
The site of action is the endogenous cannabinoid receptor in the brain,
the CB1 receptor, has been discovered, and the distribution of this
receptor has been mapped.
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Common Features of Addiction
Cannabis
Brain mechanisms:
The hippocampus contains a large concentration of THC receptors.
Marijuana is known to affect people’s memory by disrupting the normal
functioning of the hippocampus.
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Common Features of Addiction
Cannabis
Long-term damage:
The effects of long-term marijuana use include bronchitis, increased
risk of lung cancer, poor ability to control the use of the drug, minor
impairments of attention and memory, and slower choices in decision
making tasks.
Cognitive impairments from long-term use appear to be subtle.
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Heredity and Drug Abuse
Heritability Studies of Humans
In general, studies have found that the heritability of smoking is just as
strong as that of alcoholism.
A twin study found that alcoholism and nicotine dependence have
genetic factors in common, which explains why alcoholics are often
addicted to nicotine.
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