Lecture 8: Pharmacology of Drugs of Abuse

Question 1

3 ways drugs are classified into schedules

Answer 1

1. medical use
2. abuse potential
3. likelihood of dependence when abused

Question 2

Requirements for schedule I

Answer 2

1. no accepted medical use
2. lack of accepted safety under medical supervision
3. high potential for abuse

Question 3

requirements for schedule II

Answer 3

substances with high potential for abuse, which may lead to severe psychological or physical dependence

Question 4

requirements for schedule III

Answer 4

less potential for abuse and may have moderate or low physical dependence or high psychological dependence. includes codeine, ketamine, suboxone

Question 5

requirements for schedule IV

Answer 5

low potential for abuse e.g. xanax

Question 6

requirements for schedule V

Answer 6

low potential for abuse and primarily containing limited quantities of certain opiates

Question 7

estimated cost of drug use to society in lost productivity, health care expense, and crime-related and other costs exceeds ___

Answer 7

half a trillion dollars annually

Question 8

drug use is highest among people in their ___

Answer 8

late teens and twenties

Question 9

drug use is ___ among people in their fifties

Answer 9

increasing

Question 10

abuse of prescription stimulants is ____

Answer 10

increasing

Question 11

nosology

Answer 11

classification of diseases

Question 12

differences in DSM5 SUD

Answer 12

diagnose people by looking at continuum of severity, + dual diagnosis

Question 13

who discovered the reward circuit in the brain?

Answer 13

olds and milner in 1950s

Question 14

rats preferred ___ to ____

Answer 14

intracranial self stimulation (ICSS) to other natural reinforcements

Question 15

drugs hijack normal mechanisms underlying ___

Answer 15

reinforcement learning

Question 16

5 areas drug abuse acts on

Answer 16

1. VTA
2. nucleus accumbens
3. hippocampus
4. amygdala
5. prefrontal cortex

Question 17

what do VTA and NA mediate?

Answer 17

acute pleasurable sensation

Question 18

hippocampus and amygdala are responsible for ___

Answer 18

memories of pleasure

Question 19

PFC impairments mediate ___

Answer 19

long term changes involved in loss of control, relapse

Question 20

pathway of drug reinforcement (starts with, +4)

Answer 20

VTA

1. amygdala
2. nucleus accumbens
3. PFC
4. ACC

Question 21

Nora Volkow discovered ___

Answer 21

significant relationship between intensity and duration of rush with cocaine and degree to which drug blocks dopamine reuptake

Question 22

DA release is related to the size of a ____, which controls ____

Answer 22

1. prediction error

2. error-driven learning

Question 23

error can be conceived either as the difference between ___ or difference between ____

Answer 23

1. correct and actual response

2. predicted and actual outcome

Question 24

DA release is relatd to the error term in ___

Answer 24

temporal-difference learning

Question 25

when something good happens that is unexpected, ___

Answer 25

more dopamine is released than if the good thing was expected

Question 26

4 variables making someone prone to addiction

Answer 26

1. stress 2. genetic background 3. environment 4. social context

Question 27

___ is profoundly altered by chronic drug abuse. how?

Answer 27

frontal lobe; lower metabolic rate in frontal lobe

Question 28

____ occurs after long term drug abuse

Answer 28

cortical hypofrontality; decreased cerebral blood

Question 29

fewer dopamine receptors appear in ____

Answer 29

NAc; homeostatic down regulation

Question 30

frontal lobes become ___ to drug-related stimuli

Answer 30

sensitized

Question 31

over time, ____ produce a greater response in reward pathway than rewarding stimuli themselves

Answer 31

stimuli that predict drugs

Question 32

9 structures involved in addiction

Answer 32

1. frontal cortex 2. prefrontal cortex 3. parietal cortex 4. OFC 5. VTA 6. basal ganglia 7. nucleus accumbens 8. amygdala 9. hippocampus

Question 33

3 major conditions that trigger relapse

Answer 33

1. reexperience with drug 2. conditioned drug cues 3. stress

Question 34

6 structures involved in glutamatergic addiction

Answer 34

1. medial prefrontal cortex 2. OFC 3. anterior cingulate cortex 4. thalamus 5. hippocampus 6. amygdala

Question 35

main role of glutamate in addiction

Answer 35

release glu into NAc and VTA; craving mediated as increased glu activity within reward circuit

Question 36

____ protein accumulates in ___ after chronic use of drugs

Answer 36

delta FosB | NAc

Question 37

several drugs of abuse also reduce ____

Answer 37

neurogenesis

Question 38

what parts are involved in signaling significance or desirability of stimulus in motivational circuits? (2)

Answer 38

1. NAc | 2. amygdala

Question 39

what part provides incentive for obtaining reward in conditioning/learning pathways?

Answer 39

hippocampus

Question 40

what part strengthens behaviors that obtain reward and weaken inhibitory processes?

Answer 40

frontal lobe

Question 41

how high is the heritability of addiction?

Answer 41

0.3-0.7

Question 42

chromatin (2 components)

Answer 42

histones and DNA

Question 43

histones

Answer 43

spools of protein around which strands of DNA are wound; thin tail extends

Question 44

charge of histones and effect

Answer 44

positive; helps attract negatively charged DNA

Question 45

nucleosome

Answer 45

eight histones plus 166 base pairs of DNA

Question 46

DNA methylation

Answer 46

adds methyl group to DNA; alters expression of genes by activating or repressing

Question 47

epigenetic factors; where they bind and what they effect

Answer 47

biochemical molecules that bind to histone tails; affect how tightly DNA molecule is wound around histones

Question 48

DNA that is loosely bound is ___, DNA tightly wound is ____

Answer 48

easily activated | not easily activated

Question 49

5 biochemical mechanisms of epigenetic process

Answer 49

1. methylation 2. acetylation 3. phosphorylation 4. ubiquitination 5. sumoylation

Question 50

when histones are tightly compacted, genes on DNA are ___

Answer 50

hidden within nucleosome and not easily exposed

Question 51

to turn genes on and off, the structure of ___ has to be altered

Answer 51

chromatin

Question 52

DNA methylation ___, whereas demethylation ___

Answer 52

1. silences genes | 2. opposite effect

Question 53

histone acetylation ___, whereas histone deacetylation ____

Answer 53

enhances gene transcription | opposite effect

Question 54

enzyme involved in methylation

Answer 54

DNA methyltransferase, DNMT

Question 55

enzyme involved in demethylation

Answer 55

DNA demethylase

Question 56

enzyme involved in histone acetylation

Answer 56

histone acetyltransferase, HAT

Question 57

DNA methylation can lead to ___

Answer 57

histone deacetylation

Question 58

drugs of abuse cause changes in ___

Answer 58

histone acetylation

Question 59

expression of ___ is under epigenetic control

Answer 59

expression of delta FosB; makes it more responsive on subsequent reexposure to drug

Question 60

3 methods of pharmacotherapy for SUD

Answer 60

1. agonist substitution 2. partial agonist substitution 3. antagonists

Question 61

opioid addiction agonist

Answer 61

methadone

Question 62

nicotine addiction agonist

Answer 62

nicotine lozenges, gum, patches

Question 63

alcohol addiction agonist

Answer 63

antabuse (disulfiram); acetaldehyde buildup

Question 64

partial agonist for opioids

Answer 64

buprenorphine

Question 65

partial agonist for nicotine

Answer 65

varenicline

Question 66

3 opiate antagonists

Answer 66

1. naloxone 2. naltrexone 3. nalmefene

Question 67

GABA-__ agonists, like ___, can reduce reinforcing effects of drugs

Answer 67

B; baclofen; anticonvulsants

Question 68

there are ___ on GABA neurons in VTA, and their activation ___. what can have similar effect?

Answer 68

mu opioid receptors; disinhibits DA neurons | CB1 receptors

Question 69

kappa receptor stimulation ___ and can result in ___

Answer 69

reduces activity in NAc; leads to dysphoria

Question 70

what makes naltrexone effective?

Answer 70

blocks actions of endorphins released by alcohol and mediate pleasure; very high affinity antagonist of mu opioid receptor

Question 71

how can vaccines help with relapse prevention?

Answer 71

1. stimulate production of drug specific antibodies | antibodies bind to drug molecules and keep them from crossing BBB