28. Introduction to Addictions

Question 1

Is physiological tolerance and withdrawal enough to describe someone as addicted?

Answer 1

NO, tolerance/withdrawal are not enough to diagnose an addiction. Addiction requires other criteria such as: loss of control, substance use despite adverse health/social/financial effects, use under dangerous conditions, failing to live up to obligations, etc

Question 2

what is classical conditioning?

Answer 2

involves a previously irrelevant stimulus (ie, bell with Pavlov’s dog) that becomes meaningful by association with a reward (dog food). Plays a huge role in drug use and relapse.

Question 3

what is operant conditioning?

Answer 3

involves both positive and negative reinforcement.

Question 4

what is positive reinforcement?

Answer 4

INCREASES the frequency of behavior because the behavior makes a good feeling start.

Question 5

what is negative reinforcement?

Answer 5

INCREASES the frequency of behavior because the behavior makes a BAD feeling END.
note different from punishment which will DECR the frequency of behavior

Question 6

very generally, how do addictive drugs activate the reward pathway?

Answer 6

Reward Circuit: Dopaminergic neurons in ventral tegmentum; these project up to the nucleus accumbens and from there, access the higher brain centers.

Question 7

generally, what is the cycle of addiction?

Answer 7

Drug euphoria –> neuro-adaptation –> drug craving –> brain reward –> back to euphoria and adaptation

Question 8

what are the adaptations (2 main ones) that the brain uses in response to drug use?

Answer 8

neuro-adaptations:
1. tolerance
2. upregulate the anti-reward system
unfortunately, the net result is that, after taking drugs, something that should be naturally rewarding (food, sex, exercise) now is much less rewarding.

Question 9

What is the anti-reward system, and why do we need it?

Answer 9

Turns off the reward, so that we will do the behavior again to prompt another reward. Basically a decay of the reward signal.

Question 10

in order of speed of delivery/effect, what are the various routes of drug administration?

Answer 10

oral (slow due to first pass effect)
intranasal
IV
intrapulmonary (bypasses the venous system)

Question 11

Why can addiction be considered a disease? (3 reasons)

Answer 11

1. addiction has identifiable symptoms
2. has a predictable course
3. has treatment that is as successful as that for other diseases (diabetes, asthma)

Question 12

3 different causes of relapse, in general terms?

Answer 12

cue-induced
stress-induced
drug-induced

Question 13

what would be an example (in mouse model) of a cue induced relapse?

Answer 13

train mouse to self-administer drugs in a cage with a checkered floor. then un-addict the mouse.
mouse will try again to administer the drug when placed on a checkered floor.

Question 14

human analog to cue-induced relapse?

Answer 14

people, places, things

Question 15

what would be an example (in mouse model) of a stress induced relapse?

Answer 15

train mouse to self-administer drugs. then un-addict the mouse.
Stress mouse (foot shock): mouse will attempt to self-administer again.

Question 16

human analog to stress-induced relapse?

Answer 16

kinda obvious: stress

HALT = hungry, angry, lonely tired

Question 17

what would be an example (in mouse model) of a drug induced relapse?

Answer 17

train mouse to self-administer drugs. then un-addict the mouse.
Give mouse drug again unexpectedly. mouse will attempt to self-administer again.

Question 18

human analog to drug-induced relapse?

Answer 18

having one drink and relapsing completely

Question 19

define a full agonist

Answer 19

bind/activate the receptor in a dose-dependent way. linear response until max is achieved.

Question 20

most abused opioids are what kind of agonist?

Answer 20

full agonist

Question 21

define a partial agonist

Answer 21

bind/activate the receptor, but increased dose is less effective than with a full agonist.
max point is lower than a full agonist –> diminishing returns

Question 22

what kind of agonist is methadone?

Answer 22

full. think Porsche

Question 23

what kind of agonist is buprenorphine?

Answer 23

partial. think Penske moving truck

Question 24

what kind of agonist is naloxone?

Answer 24

antagonist!! think gum in a lock. blocks agonists

Question 25

how does positive reinforcement work to perpetuate drug use?

Answer 25

direct: you use drug, you get euphoria

Question 26

how does negative reinforcement work to perpetuate drug use?

Answer 26

kind of indirect: you use drug, you avoid the misery of withdrawal

Question 27

methadone works on what kind of receptors?

Answer 27

mu opioid receptors.

Question 28

methodone: how used to stop negative reinforcement?

Answer 28

it has a long half-life, so pts can take it once/day and not have withdrawal. extinguishes the effect of negative reinforcement.

Question 29

methodone: how used to stop positive reinforcement?

Answer 29

give people same dose as heroin, then rachet up dose to way past the heroin dose they used. now they can't afford to get high with heroin. stops positive reinforcement (can't afford heroin high)

Question 30

methodone: we use it to get people off what drug?

Answer 30

heroin (and other opiates? unsure)

Question 31

Buprenorphine: works on what receptors?

Answer 31

mu opioid receptors

Question 32

Buprenorphine: how does it stop positive reinforcement?

Answer 32

binds really tightly to mu opioid receptor. nothing else (no other drug) will displace it. even if you take heroin, won't get high.

Question 33

Buprenorphine: how does it stop negative reinforcement?

Answer 33

it has a long half-life, so pts can avoid withdrawal. extinguishes the effect of negative reinforcement.

Question 34

why can addiction be considered a BRAIN disease?

Answer 34

1. all addictive substances act on one area of brain (ventral tegmental tract or reward system) 2. prolonged use causes changes in brain function that persist after end of drug-taking 3. addicted brain is different from non-addicted brain.

Question 35

(handout) define social use of a substance

Answer 35

use without meeting criteria for either abuse or dependence

Question 36

(handout) define substance abuse

Answer 36

maladaptive pattern of use leading to impairment/distress defined as one of these within 12 months: - failure to fulfill major obligations - use even when physically hazardous - use-related legal problems - use despite recurrent social/interpersonal problems that it is causing

Question 37

(handout) define substance dependence

Answer 37

(essentially this is addiction: more severe than substance abuse) three or more items from a long list within 12 months. List includes tolerance, withdrawal, interference with life activities, loss of control of use.