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Page 1: Copyright (c) Allyn & Bacon 2004 1 Chapter 16 Drug Abuse This multimedia product and its contents are protected under copyright law. The following are

Copyright (c) Allyn & Bacon 20041

Chapter 16

Drug Abuse

This multimedia product and its contents are protected under copyright law. The following are prohibited by law: any public performance or display, including transmission of any image over a network, preparation of any derivative work, including the extraction, in whole or in part, of any images; any rental, lease or lending of the program.

Page 2: Copyright (c) Allyn & Bacon 2004 1 Chapter 16 Drug Abuse This multimedia product and its contents are protected under copyright law. The following are

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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

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

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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Commonly Abused Drugs

Opiates

Cocaine and Amphetamines

Nicotine

Alcohol and Barbiturates

Cannabis

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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

Periaqueductal gray matter (PAG):• Stimulation of the PAG opiate receptors cause

analgesia.

Preoptic area:• Stimulation of the preoptic area opiate receptors

cause hypothermia (reduction of body temperature).

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Common Features of Addiction Neural Basis of Reinforcing Effects

Mesencephalic reticular formation:• Stimulation of the opiate receptors in the

mesencephalic reticular formation cause sedation.

Ventral Tegmental area (VTA) and the nucleus accumbens:• Stimulation of the opiate receptors in the VTA

and nucleus accumbens play a role in the reinforcing effects of opiates.

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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 buttons-presumably 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.