Drug Addiction and the Brain’s Reward System

Question 1

drug

Answer 1

An exogenous substance that, when absorbed into the body of a living organism, alters normal bodily function.

Question 2

psychoactive drug

Answer 2

Drugs that influence subjective experience and behavior by acting on the nervous system.

Question 3

Drugs are typically administered in one of four ways:

Answer 3

• Oral Ingestion (e.g. alcohol). Unpredictable: rate depends on presence of foods, etc.
• Injection (e.g. heroin). Used in medical practice because the effects can be large, rapid and predictable. subcutaneously (SC), into the fatty tissue just below the skin, intramuscularly (IM), into the large muscles; or intravenously (IV), directly into the veins at points where they run just beneath the skin, which causes the risk of allergies, impurities in the drugs, damage to veins.
• Inhalation (e.g., tobacco) through the capillaries in the lungs. Dosage is difficult; can be damage to airways and lungs after chronic use.
• Absorption through Mucous Membranes (e.g. cocaine)

Question 4

Psychoactive Drugs influence the CNS in many ways, including:

Answer 4

• Binding to pre- and postsynaptic receptors.
• Influencing synthesis, transport, release, or deactivation of neurotransmitters.
• Influencing the chain of chemical reactions elicited by the activation of postsynaptic receptors.

Question 5

Most drugs are deactivated by

Answer 5

enzymes synthesized by the liver.

Question 6

Drug Metabolism

Answer 6

Process by which liver enzymes convert active drugs to non-active forms. Typically enzymes convert drugs into a more hydrophilic form, preventing the drug from being able to pass through the lipid membranes of cells.

Question 7

Drug Elimination

Answer 7

Small amounts of some psychoactive drugs are passed out of the body in urine, sweat, feces, breath, and mother’s milk.

Question 8

Drug Tolerance

Answer 8

State of decreased sensitivity to a drug that develops as a result of exposure to it.

Question 9

Drug tolerance can be shown in two ways:

Answer 9

• A given dose of a drug has LESS of an effect than that before exposure to it.
• A HIGHER dose of a drug is required to produce the same effect.

Question 10

Drug Sensitization

Answer 10

A shift of the dose-response curve to the left.

Question 11

Cross Tolerance

Answer 11

One drug can produce tolerance to other drugs that act by the same mechanisms.

Question 12

Metabolic Tolerance

Answer 12

Drug tolerance that results from changes that reduce the amount of the drug getting to its sites of action. E.g. liver increases the production of enzymes that metabolize a drug.

Question 13

Functional Tolerance

Answer 13

Drug tolerance that results from changes that reduce the reactivity of the sites of action to the drug. E.g. reduction in the number of receptors for a drug.

Question 14

Tolerance to psychoactive drugs is largely

Answer 14

functional. In functional tolerance, there can also be less binding of the drug to receptors, or less effect on the cells.

Question 15

Withdrawal symptoms

Answer 15

Occurs when significant amounts of a drug that have been in the body for a period of time suddenly decrease. Withdrawal effects are often opposite the initial effects of the dru.

Question 16

physically dependent

Answer 16

Individuals that suffer withdrawal reactions when they stop taking a drug.

Question 17

it is thought that tolerance and withdrawal effects are related:

Answer 17

The same mechanism that produces tolerance produces the opposite withdrawal effect.

Question 18

drug exposure leads to

Answer 18

the development of adaptive neural changes that produce tolerance by counteracting the drug effect.

Question 19

drug withdrawal:

Answer 19

with no drug to counteract them, the neural adaptations produce withdrawal effects opposite to the effects of the drug.

Question 20

Contingent Drug Tolerance

Answer 20

Tolerance develops only to drug effects that are actually experienced. If the drug is taken after the effect, not tolerance develops.

Question 21

Conditioned Drug Tolerance

Answer 21

Tolerance effects are maximally expressed only when a drug is administered in the same situation in which it has previously been administered.

Question 22

Conditioned withdrawal effect:

Answer 22

tolerance effects are maximally expressed only when a drug is administered in the habitual conditions. being in a room used for drugs, but not having drugs. The compensatory effects would be triggered but since there is no drugs, opposite withdrawal effect would be elicited.

Question 23

addiction

Answer 23

Habitual drug use despite its adverse effects on health, social life, and despite repeated efforts to stop. Drug addicts are habitual drug users. Not all habitual drug users are addicts.

Question 24

Is addiction the same thing as physical dependence?

Answer 24

no, drug addicts will renew drug taking even after withdrawal effects have subsided.

Question 25

physical dependence theory

Answer 25

dependence due to pain of withdrawal. Addicts caught in a cycle of drug taking, withdrawal, drug taking to relieve withdrawal. TREATMENT: gradually withdrawing drug use.

Question 26

detoxified addicts

Answer 26

No longer have drugs in their system and do not experience withdrawal symptoms.

Question 27

the physical dependence theory does not explain why…

Answer 27

addicts relapse long after detoxification. individuals begin using drugs in the first place. addictions develop to drugs that do not produce severe withdrawal symptoms (e.g., cocaine, amphetamines).

Question 28

positive incentive theories

Answer 28

The primary factor in most cases of addiction is the craving for a drug’s pleasurable effects. Addicts generally use more drug than that needed to relieve withdrawal symptoms. Some pleasure could be indirect, like disinhibition (alcohol in parties). Positive incentive values increases with use: Tolerance to aversive effects, rather than to pleasurable effects. Sensitization to positive incentive values.

Causes of relapse: STRESS leads to use of drugs. priming. exposure to cues associated with drug.

Question 29

positive incentive theories must explain…

Answer 29

the difference between the hedonic value (actual pleasure experienced) and the positive incentive value (wanting) of the drug. Drug users crave drugs, but enjoyment often declines. the transition from being a drug user to becoming a drug addict.

Question 30

reward circuit

Answer 30

Olds and Milner (1954) discovered brain “pleasure centers.” Proposed that the same brain regions are activated by natural rewards, such as food, water, and sex. Many species will work for stimulation of brain “pleasure centers.” Drug use may be reinforced by acting on this circuitry.

Question 31

Intracranial Self-Stimulation (ICSS)

Answer 31

A rat pressing a lever to obtain rewarding brain stimulation.

Question 32

Mesotelencephalic Dopamine System

Answer 32

Dopaminergic neurons projecting from two midbrain areas to telencephalon. Modulatory effect, contrast with sensory pathways, which are very specific.

Question 33

Nigrostriatal pathway

Answer 33

Substantia nigra neurons projecting to dorsal striatum (basal ganglia). Associated with Parkinson’s Disease.

Question 34

Mesocorticolimbic pathway

Answer 34

Ventral tegmental area neurons projecting to cortical and limbic sites, including the nucleus accumbens (including septum, amygdala, olfactory tubercle, nucleus accumbens, prefrontal neocortex, and limbic cortex). This is the major “reward” pathway for ICSS, natural rewards, and addictive drugs.

Question 35

mapping studies (evidence that the mesotelencephalic pathway plays an important role in ICSS)

Answer 35

Sites that induce self-stimulation are part of this system. Self-stimulation sites that do not contain dopaminergic neurons project to the mesotelencephalic dopamine system.

Question 36

Cerebral dialysis studies (evidence that the mesotelencephalic pathway plays an important role in ICSS)

Answer 36

samples of extracellular fluids are collected for about 15 min and analyzed chemically. Increase in dopamine release seen in the mesocorticolimbic pathway following self-stimulation.

Question 37

other evidence that the mesotelencephalic pathway plays an important role in ICSS

Answer 37

Dopamine agonists tend to increase self-stimulation and antagonists to decrease self-stimulation. Lesions of the mesocorticolimbic pathway disrupt self-stimulation. Lesions in one side reduced self-stimulation to electrical pulses in that side but not to stimulation of the other side.

Question 38

Drug self-administration paradigm (way to measure drug positive incentive in animals)

Answer 38

Lab animals press a lever to inject drugs into themselves either IV or through cannulas (thin tubes) implanted in the brain.

Question 39

Conditioned place-preference paradigm (way to measure drug positive incentive in animals)

Answer 39

Lab animals choose to spend more time in the cage compartment where drugs were administered, compared to a compartment not associated with drug administration.

Question 40

Evidence of the Involvement of Dopamine in Drug Addiction

Answer 40

• Dopamine’s role suggested by self-stimulation studies.
• Dopamine antagonists interfere with self-stimulation of, or conditioned place preference for, several addictive drugs, and reduce the reinforcing effects of food.
• the “highs” experienced by addicts was correlated with the degree to which cocaine prevented the reuptake of dopamine by binding to the dopamine transporters.
• Nucleus accumbens appears to play a primary role.

Question 41

cocaine blocks the

Answer 41

reuptake of dopamine by dopamine transporters located in the presynaptic terminal. monoamino oxidase (MAO) catalyzes the oxidation of monoamines. deactivates dopamine inside the presynaptic neuron.

Question 42

Positron emission tomography (PET) studies

Answer 42

radioactively labeled cocaine binds to these transporters and the “high” is proportional to the amount of binding (at least 50% binding is required for experiencing a “high”).

Question 43

Evidence of the Involvement of the Nucleus Accumbens in Drug Addiction

Answer 43

• Animals self-administer microinjections of addictive drugs into NA.
• Microinjection of drugs into NA produce conditioned placed preferences
• Lesion of the NA or ventral tegmental area – no drug self-administration or drug-related place preference.
• Both self-administration of addictive drugs and natural reinforcers result in increased levels of dopamine in the NA.

Question 44

reward

Answer 44

Ventral tegmental neurons fire in response to a stimulus at a rate proportional to its reward value.

Question 45

expectation of reward

Answer 45

Neutral stimuli that predict a reward can trigger dopamine release in the NA ( at the beginning of conditioning experiments).

Question 46

current view on dopamine release as a reward or expectation of reward

Answer 46

An increase in the activity of dopaminergic neurons in the ventral tegmental area occurs:
when a conditional stimulus predicts a reward. when a reward is presented in an unpredictable fashion. it appears that dopamine is involved in the expectation of reward rather than the reward itself.

Question 47

stress (cause of relapse)

Answer 47

drug use as a coping mechanism.

Question 48

priming (cause of relapse)

Answer 48

a single exposure to previously used drug leads to a relapse.

Question 49

environmental cues (cause of relapse)

Answer 49

Conditioned withdrawal effect. Returning to place where drugs once were taken (or even thinking about drug) causes conditioned compensatory responses, craving, and relapse.

Question 50

Initial drug taking (structures that mediate addiction)

Answer 50

involves activation of the mesocorticolimbic pathway (nucleus accumbens), prefrontal lobes (decision to take drug), and amygdala (positive or negative emotional reactions to the drug taking).

Question 51

Craving and compulsive drug use (structures that mediate addiction)

Answer 51

Involves activation of the dorsal striatum and hypothalamic stress circuits. recent studies suggest the insular cortex.

Question 52

relapse (structures that mediate addiction)

Answer 52

stress (mediated by hypothalamic stress circuits). priming doses (mediated by prefrontal cortex). conditional cue-induced relapse (mediated by amygdala).

Question 53

Functional imaging studies have implicated the

Answer 53

insula in conscious desires, such as food craving and drug craving.

Question 54

is dopamine necessary for addiction to develop?

Answer 54

a study shows that while dopamine is crucial for morphine-induced locomotion effects, dopamine is not required for morphine-induce reward measured by conditioned place preference.

Question 55

five most commonly abused drugs in the united states

Answer 55

tobacco, alcohol, marijuana, cocaine, and opiates.

Question 56

some reasons to avoid substance abuse

Answer 56

• Alcohol is a key factor in more than 60 % of assaults and over half of murders or attempted murders in the United States.
• Over 40 percent of convicted rapists say they were under the influence of alcohol or other drugs at the time of their crime.
• Almost two-thirds of reported child abuse and neglect cases in New York City have been linked to alcohol or drug use by the parent.
• Up to 35 percent of suicide victims have a history of alcohol abuse or were drinking shortly before they killed themselves.

Question 57

Conditioned Withdrawal Effects

Answer 57

are the effects that are elicited by the drug environment or by other drug-associated cues.

Question 58

At first, some puzzling observations suggested that lever pressing after lateral hypothalamic and septal stimulation was different than pressing for natural rewards (food, water, sex, etc.):

Answer 58

The instant that electrical pulses were stopped, rats stopped pressing the lever immediately, not gradually , showing a rapid rate of extinction. After stopping stimulating, rats would not immediately start after being returned to the cage; the operator had to get them started again (priming).

Question 59

However, further research has revealed that pleasure centers mediating self-stimulation are related to natural reward circuits:

Answer 59

1. Brain stimulation through electrodes that mediate self-stimulation often leads to natural motivated behaviors if the appropriate objects are present: food, water, etc.
2. Increasing natural motivation by, for example, food or water deprivation often increases the rate of electrical self-stimulation.

Question 60

The projection from neurons in the ventral tegmental area to the nucleus accumbens has been most often implicated in the

Answer 60

rewarding effects of brain stimulation, natural rewards, and addictive drugs.

Question 61

The idea that the mesocorticolimbic pathway is involved in drug addiction is supported by:

Answer 61

1. Evidence that the pleasurable effects of drugs, rather than the alleviation of withdrawal symptoms, are the major factors in addiction.
2. Evidence that the mesocorticolimbic pathway plays an important role in intracranial self-stimulation.
3. Evidence that the mesocorticolimbic pathway is involved in the effects of natural rewards (food, water, sex, etc).

Question 62

In non-addicts, increased levels of dopamine in the

Answer 62

nucleus accumbens caused by IV injections of amphetamine are associated with an increase in their experience of euphoria.

Question 63

lesions of the nucleus accumbens have failed to

Answer 63

block the relapse in opiate addicts, confirming that other structures play a role in addiction.

Question 64

What can be done for addicts?

Answer 64

Perhaps one possibility will be to develop selective dopamine antagonists that reduce the positive-incentive value of drugs in addicts without reducing the positive-incentive value of natural motivated behaviors.