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Psychology of Addiction > Midterm 1 > Flashcards

Midterm 1 Flashcards

1
Q

Ways of Knowing intuition:

A

“I know it’s true because it makes sense (e.g., logic, street smarts)

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2
Q

Ways of Knowing tenacity:

A

“I know it’s true because it’s always been that way”

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3
Q

Ways of Knowing authority:

A

“I know it’s true because the Bible, the Koran, the President, the King, the Queen, etc. tells me it’s true”

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4
Q

Ways of Knowing science:

A

“It’s true insofar as measurable evidence from reliable instruments verify it repeatedly”

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5
Q

DSM addiction categories focus exclusively on specific substances used and ____, with no consideration of ____

A

topographies of behavior, etiopathophysiology

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6
Q

In the DSM tolerance is characterized by

A

(a) a need for markedly increased amounts of the substance to achieve intoxication or desired effect
(b) markedly diminished effect with continued use of the same amount of the substance

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7
Q

In the DSM withdrawal is characterized by

A

(a) the characteristic withdrawal syndrome for the substance (e.g., for cocaine, increased sadness, fatigue, hypersomnia, appetite)
(b) the same (or a closely-related) substance is taken to relieve or avoid withdrawal symptoms (e.g., for alcohol, benzodiazepines [e.g., Xanax] might be substituted)

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8
Q

What is the single most abused substance?

A

alcohol

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9
Q

in recent years, ___ use has trended down, while ____ use has trended up

A

cocaine, prescription opioid

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10
Q

there is a myth, even among physicians, that risk of addiction is low during ____ especially when _____ are used; this does not hold up to empirical scrutiny

A

prolonged opioid therapy for pain, controlled release compounds

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11
Q

in 2016, ___ was the leading cause of overdose in the US

A

fentanyl

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12
Q

Heroin purity is unpredictable, and much stronger opiates ___ and ___ are sometimes cut in

A

fentanyl, carfentanil

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13
Q

much of the vulnerability to SUDs (Substance Use Disorders) is ____

A

inherited

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14
Q

Having an alcoholic parent increases the risk for alcoholism by 400% and having 2 alcoholic parents increases the risk for alcoholism by over 600%

This does not change when offspring of alcoholics are reared in ____

A

non-alcoholic homes

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15
Q

For alcohol, age at first drink is determined largely ___

However, dependence is largely ___

A 
by environment (deviant peers), 
heritable (capable of being passed from one generation to the next; hereditary)
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16
Q

True or false: Genetic vulnerability alone cannot explain addiction

A

True

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17
Q

The “War on Drugs” was initiated by President ___ in what year?

A

President Richard Nixon in 1971

Many believe incorrectly that the “War on Drugs” was initiated by President Ronald Reagan in the early 1980s

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18
Q

Who stated that drug use was “Public Enemy Number 1”

A

President Richard Nixon in 1971

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19
Q

In 1973 Nixon created what agency? What was the budget?

A

Drug Enforcement Administration (DEA) hiring 1470 agents and with a budget of about $75 million

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20
Q

Today, the DEA has how many agents? How much of a budget? How much has it increased?

A

5000 agents

budget of $2.03 billion–> a 270-fold increase

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21
Q

In an interview with Dan Baum in 1994, ____ Assistant to the President (Nixon) for Domestic Affairs, described how the War on Drugs was invented for ____

A

John Ehrlichman,

subversive political purposes

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22
Q

In 1994, John Ehrlichman, Assistant to the President (Nixon) for Domestic Affairs, said the war on drugs was created to go against 2 Nixon White House enemies. Who are they?

A

The antiwar left and Black people

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23
Q

Political self-serving means (expediency) also played a central role in Reagan’s ____ agenda, which he campaigned on and sold to the public in a national radio address on September 11, ___

A

“Get Tough on Crime”

1982

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24
Q

Reagan cut what he called, “the spider’s web of welfare”, including (3)

A
  1. the Aid to Families with Dependent Children (AFDC) program (by 50%)
  2. the Supplemental Nutrition Assistance Program (food stamps), and
  3. Medicaid (all who lost AFDC funding lost Medicaid eligibility too)
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25
Q

In 1984 the Reagan Administration created the United States Sentencing Commission and implemented the Sentencing Reform Act which did what? What did this lead to?

A

abolished parole in the federal prison system and established new, more strict federal sentencing guidelines
this lead to a huge spike in incarceration rates

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26
Q

There are currently about 2.3 million people in the US in the prison system at a cost of over ___ annually, and we incarcerate up to ___ of our population than other Western cultures

A

$80 billion

10x more

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27
Q

Almost ___ are incarcerated for non-violent drug-related crimes, primarily ___

A

50%

possession

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28
Q

1986 legislation signed by President Reagan that imposed federal ____ for drug offenses

A

mandatory minimum sentences

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29
Q

Blacks use drugs at ___ rate as Whites, but they are far more likely to be arrested and incarcerated

A

the same

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30
Q

Blacks comprise ___% of US drug users, but ___% of those arrested for drug violations, __% of those convicted, and __% of those sentenced to prison

A

15%
40%
60%
75%

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31
Q

Problems with disparities in mandatory sentencing (4)

A
  1. cocaine is cocaine is cocaine (powder is converted to crack with water and baking soda)
  2. dealers are more likely to transport and sell powdered cocaine
  3. Blacks are disproportionately poor, and poor people are more likely to use crack, BUT…
  4. police (arrests) and judges (convictions) are far harsher on Blacks than on whites:
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32
Q

Is the war on drugs over?

A

No The War on Drugs is STILL being levied against our most vulnerable members of society, in poor urban neighborhoods that are disproportionately Black and do not have resources to cope

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33
Q

Institutional racism

A

“policies and practices that are built into the structures of various social institutions that continue to operate even without the active support and maintenance of individuals”

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34
Q

Direct racism:

A

policies that are purposefully designed to have discriminatory effects
EX: the original motivation for the war on drugs

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35
Q

Indirect racism:

A

practices that have disproportionate effects on people of different races without any intent to discriminate

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36
Q

An example of indirect racism

A

increased police presence in urban poor urban neighborhoods can result in more young Black males being arrested than Whites who commit similar crimes elsewhere

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37
Q

States have little agency to override federal guidelines, but some are addressing the issue to the extent that they can. In 2018 in Ohio, the Neighborhood Safety, Drug Treatment, and Rehabilitation Amendment Initiative failed; it would have (4)

A
  1. changed drug possession felonies to misdemeanors
  2. prohibited prison sentences for technical probation violations
  3. expanded the ability to earn up to 25% off a prison sentence through rehabilitative programming, and
  4. redirected funds saved from reduced incarceration to drug treatment and victims’ services
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38
Q

addiction cannot be understood at any single level of analysis, neural, behavioral, emotional

neural:

A

sensitization of brain regions to drug cues (e.g., greater dopaminergic neural reactivity in the striatum); down-regulation of brain function via allostatic load

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39
Q

addiction cannot be understood at any single level of analysis, neural, behavioral, emotional

Behavioral:

A

use of larger amounts or over longer periods of time

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40
Q

addiction cannot be understood at any single level of analysis, neural, behavioral, emotional

emotional:

A

development of craving, a strong emotional urge to use

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41
Q

Neural Aspects of Addiction brain dopamine (DA) systems (3-4 depending on how they are parsed)
tuberoinfundibular pathway:

A

originates in the arcuate nucleus of the hypothalamus and projects to the pituitary gland; important for hormone regulation

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42
Q

Neural Aspects of Addiction brain dopamine (DA) systems (3-4 depending on how they are parsed)
nigrostriatal pathway:

A

originates in the substantia nigra, pars compacta, and projects to the dorsal striatum (caudate, putamen); important for movement but also plays a role in addiction

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43
Q

Neural Aspects of Addiction brain dopamine (DA) systems (3-4 depending on how they are parsed)
mesolimbic pathway:

A

originates in the ventral tegmental area (VTA), and projects forward to the ventral striatum, the nucleus accumbens, the amygdala, and the bed nucleus stria terminalis; implicated in all reward-motivated behavior (e.g., food-seeking, self-preservation, sexual reproduction)

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44
Q

Neural Aspects of Addiction brain dopamine (DA) systems (3-4 depending on how they are parsed)
mesocortical pathway:

A

projects forward from portions of the mesolimbic system to cortical areas including the dorsolateral PFC, the medial PFC, the anterior cingulate cortex (ACC), and the temporal cortex

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45
Q

Neural Aspects of Addiction–> brain dopamine (DA) systems (3-4 depending on how they are parsed) name them

A

tuberoinfundibular pathway, nigrostriatal pathway, mesolimbic pathway, mesocortical pathway

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46
Q

The brain dopamine (DA) systems that are subcortical (deep; “under” the cortex) and phylogenetically old

A

tuberoinfundibular pathway, nigrostriatal pathway, mesolimbic pathway,

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47
Q

The brain dopamine (DA) system mesocortical is (3)

A
  1. largely cortical
  2. is evolved fully in primates—particularly humans
  3. provides top-down regulation over impulses generated by the subcortex
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48
Q

Dorsal/superior is which direction on the brain?

A

Top (see pic)

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49
Q

Rostral/anterior is which direction on the brain?

A

front

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50
Q

Ventral/inferior is which direction on the brain?

A

bottom

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51
Q

Caudal/posterior is which direction on the brain?

A

rear

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52
Q

The subcortex is linked to

A

motivation and emotion generation

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53
Q

The cortex is linked to

A

behavior and emotion regulation

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54
Q

tonic DA activity is associated with

A

mood states

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55
Q

high tonic DA →

A

positive affectivity (affective component of euphoria)

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56
Q

low tonic DA →

A

negative affectivity, irritability (affective components of craving)

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57
Q

mesolimbic DA activity is

A

experience dependent

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58
Q

repeated phasic activation produces

A

reduced tonic activity and sensitization

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59
Q

almost all drugs of abuse produce ___ in mesolimbic DA that (often far) exceed those induced by normal reinforces (e.g., food, sex):

A

phasic increases

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60
Q

note that neural firing propagates backward in time to ___ rather than substance delivery; this is also a major component of craving

A

cue exposure

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61
Q

thus, addiction is associated with (3)

A
  1. reduced tonic neural firing, and
  2. sensitized phasic neural firing, that
  3. begins with cue exposure
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62
Q

allostatic load

A

recalibration of neural systems in response to repeated activation

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63
Q

reduced tonic neural activity may be induced by _____ or ____

A 
adaptive recalibration of neural firing (e.g., via altered numbers of DA transporters and receptors)
long term (sometimes permanent) structural damage to DA neurons
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64
Q

Behavioral Aspects of Definitions: Koob, Arends, and Le Moal (2014) define addiction as: (3)

A
  1. a compulsion to seek and take a drug
  2. loss of control in limiting intake
  3. emergence of a negative emotional state (dysphoria, anxiety, irritability) when access to the drug is prevented
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65
Q

as discussed in Lecture 1, for many years drug use has been subdivided as follows: (3)

A
  1. occasional, controlled, or social use
  2. abuse
  3. dependence/addiction
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66
Q

addiction is a ___ disease that is often characterized by ___

A

progressive, chronic relapsing

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67
Q

emotional and neural aspects of addiction cannot be disentangled fully, but they are not ____

A

isomorphic (Having a similar structure or appearance but being of different ancestry)

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68
Q

experience-dependent down-regulation of striatal DA activity produces ___ (3)

A

dysphoria
irritability
anhedonia (in some cases profound)

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69
Q

anhedonia

A

reduced motivation or ability to experience pleasure. one of the core features of depressions basically losing the ability to enjoy the things you love

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70
Q

The 2 Broad Types of “Genetics” Studies in Psychopathology Research, Including Addiction, are

A

Quantitative behavioral genetics

Molecular genetics

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71
Q

Quantitative behavioral genetics (also called behavioral genetics, quantitative genetics, biometrical genetics):

A

objective: parse variance in behavior (trait, phenotype) into heritable (both genetic and non-genetic) and non-heritable (environmental) components, using latent variable modeling

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72
Q

this parsing of variance is accomplished using ___(3)

A

twin, family, and adoption studies

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73
Q

assumptions of a basic twin study:

A
  1. monozygotic (MZ; identical) twins have nearly 100% shared genetic polymorphisms
  2. dizygotic (DZ; fraternal) twins have 50% shared genetic polymorphisms (on average)
  3. both MZ and DZ twins share many features of the environment (e.g., intrauterine development, parenting factors, SES, education, etc.)
  4. non-twin sib-sib pairs also have 50% shared genetic polymorphisms (on average), but share fewer features of the environment (different classrooms, fewer common friends, etc.)
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74
Q

ACE model:

A

Using large groups of twins and other sibs, we attempt to parse the percentage of overall variance in a phenotype (addiction symptoms) that is attributable to heritability (A^2) (IMPORTANT: heritable ≠ genetic), shared environment (C^2), and unique environment (E^2)

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75
Q

parsing environmental effects into shared and non-shared components is facilitated when the study includes identical twins (and other sib pairs) who are ___ and identical twins (and other sib pairs) who are ___

A

reared together

reared apart

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76
Q

trait-specific equal environments assumption:

A

the notion that MZ twins and DZ twins are affected in the same way by common environments is called the trait-specific equal environments assumption, and it is almost always violated (MZ twins have more similar experiences than DZ twins)

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77
Q

major limitation of ACE models:

A

do not account for GxE interactions or gene-environment correlations (rGE), which are unmeasured and subsumed within A2, resulting in overestimates of heritability

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78
Q

although peer influences account for initiation of alcohol use, heritability accounts almost entirely for ___ (2)

A

quantity and maintenance of use

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79
Q

Behavioral genetics tells us nothing about…

A

genes!

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80
Q

Molecular genetics:

A

in contrast to behavioral genetics, molecular genetics research involves direct assessment of genes

objective: identify specific genetic polymorphisms that increase vulnerability to psychopathology, including addiction

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81
Q

polymorphisms (alleles, variants) are observed in only about ___% of our 30,000 protein-coding genes

A

1%

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82
Q

single base pair (SNP) =

A

single nucleotide polymorphism

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83
Q

genotype:

A

the specific gene(s) underlying a phenotype (see below), including addiction

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84
Q

phenotype:

A

observable characteristics (physical and/or behavioral) of an organism that may or may not correspond with a particular genotype

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85
Q

Mendelian inheritance (sometimes called dominance):

A

inheritance pattern for single-gene, dominant/recessive traits

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86
Q

Mendel’s first law, also called the law of segregation, states that:

A

every offspring carries a pair of genes at each locus, one selected randomly from his/her father, and one selected randomly from his/her mother. Single gene, dominant traits produce only two phenotypes, determined by which gene is dominant.

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87
Q

very few human traits follow simple Mendelian inheritance patterns (4)

A

blood type
cystic fibrosis
Huntington’s chorea
sickle-cell disease

88
Q

human behavioral traits, including addiction, are inherited ___

A

multifactorially (via many genes)

89
Q

DD and dd genotypes are ___

A

homozygotes

90
Q

Dd and dD genotypes are ___

A

heterozygotes

91
Q

important: in only 1 of 4 cases can we infer the ___ from the ___

A

genotype

phenotype

92
Q

no human behavior, and almost no psychiatric disorder, is determined by a ___

A

single gene

93
Q

even traits that are influenced ____ by only a few genes carry unwieldy patterns of phenotypes

A

dominantly

94
Q

trihybrid phenotype=

A

three-factor cross

95
Q

Mendel’s second law (the law of independent assortment)

A

alleles of two (or more) different genes get sorted into gametes independently of one another. In other words, the allele a gamete receives for one gene does not influence the allele received for another gene.

96
Q

polygenetic inheritance/determinism (sometimes called multifactorial inheritance):

A

the influence of multiple genes on a physical or behavioral phenotype

97
Q

penetrance:

A

the proportion of individuals who carry genetic vulnerability (often called liability) and express the disorder

98
Q

Example of penetrance

A

example: almost 10% of individuals carry at least some genetic vulnerability to schizophrenia, but less than 1% develop the disorder

penetrance is therefore roughly 1/10, or 10%; this is called incomplete penetrance

99
Q

multifactorial inheritance:

A

like other psychiatric disorders, addiction is influenced by many genes, none of which are necessary or sufficient

100
Q

In psychiatric molecular genetics, we usually use one of three approaches to identify candidate genes for different disorders, including addiction: (3)

A

genetic linkage studies, genetic association studies, genome-wide association studies (GWAS)

101
Q

genetic linkage studies

A

genetic linkage refers to the tendency of alleles that are near one another on the same chromosome to be inherited together, or linked

102
Q

In genetic linkage studies we…(4)

A

a. obtain a large sample of families containing two children with a trait or disorder
b. collect genetic data from family members
c. scan broad sections of the genome in searches for genetic markers with known chromosomal locations that might be “linked” (i.e., chromosomally proximal) to a gene for the disorder
d. make educated guesses about the location of genes for complex disorders, which must be confirmed/refined in subsequent studies

103
Q

genetic linkage studies example

A

example: the gene responsible for cystic fibrosis was found by “linking” the disease to a genetic variant on the long arm of Chromosome 7 within affected families. This discovery was followed by several subsequent linkage analyses that identified the specific chromosomal location

104
Q

Problems with genetic linkage studies

A

linkage studies are expensive, produce many false leads, and have not produced strong or replicable results for psychiatric disorders

linkage studies are best suited for identifying risk loci for monogenic or oligogenic traits (i.e., traits determined by one gene or a small number of genes), whereas addiction is inherited multifactorially

105
Q

genetic association studies

A

in contrast to linkage studies, which attempt to identify allelic variants that co-segregate with the trait of interest within families, genetic association studies attempt to identify allelic variants that segregate with the trait of interest in the general population

106
Q

genetic association refers to situations in which

A

specific genes are associated with certain phenotypes

107
Q

in association studies, we

A

begin with a specific candidate gene, and then compare allelic frequencies of that gene among people with and without the disorder (case-control design)

this provides more statistical power than linkage studies

however, we need to have a good idea of where to look

108
Q

genetic association studies problem

A

association studies indicate that all vulnerability genes combined account for only a few percent of the variance any behavioral trait (including addiction) whereas behavioral genetics studies (see above) tell us that the preponderance of variance in most traits (again including addiction) is heritable (this is called the missing heritability problem):

109
Q

genome-wide association studies (GWAS)

A

hundreds of thousands of genes are “tagged” across the genome in very large samples, and searches for associations with psychopathology are conducted, using strong corrections for family-wise alpha error rates

to date, this approach has been difficult given the large sample sizes required, but progress is being made

110
Q

gene polymorphism:

A

A DNA sequence variation that is common in the population. Polymorphic variants usually do not cause life-threatening diseases directly, but may influence behavioral and other phenotypic propensities that interact with environments to confer susceptibility to disease, including psychopathology.

Gene polymorphisms are inherited

111
Q

gene mutation:

A

A change in DNA sequence away from ordinary variation observed in the population. Most have neutral effects, since much of the genome is ‘silent’. Although some are heritable, many mutations are de novo–neither expressed by nor transmitted by the parent. De novo mutations appear to play a bigger role in complex psychiatric disorders than previously thought

112
Q

Genes DO NOT control specific behaviors (e.g., addiction, aggression, suicidality). They code for ___. This occurs via ___ of deoxyribonucleic acid (DNA) into MESSENGER ribonucleic acid (mRNA), then ___ of amino acids into proteins by TRANSFER ribonucleic acid (tRNA)

A

protein expression
transcription
translation

113
Q

some genetically-derived individual differences in protein expression affect neurobiological processes such as ___in the brain, alcohol metabolism in the liver, etc

A

neurotransmission

114
Q

polygenic determinism, or multifactorial inheritance

A

no single gene controls any complex human trait. Behaviors such as impulsivity, intelligence, and depression are affected by many genes. This is called

115
Q

although genes do not determine behavior, certain gene polymorphisms confer ____ that render individuals susceptible to disease in certain environments (GxE). For example, genes associated with alcohol metabolism do not cause addiction in the absence of environmental exposure to alcohol

A

behavioral biases

116
Q

genes affect neurotransmitter system function by (2)

A

altering neurotransmitter availability via synthesis and metabolism pathways
altering efficiency of neurotransmission more directly

117
Q

MAO, COMT, DAT, and DRD4 genes are all implicated in ___ because they collectively alter DA function

A

impulsivity

118
Q

higher levels of striatal DA are associated with ___, whereas lower levels are associated with ____

A

pleasure and contentment

irritability and impulsivity

119
Q

several candidate genes for alcohol and other substance dependencies are expressed in the ___, not the brain

A

liver

120
Q

central nervous system (CNS):

A

brain and spinal cord

121
Q

peripheral (autonomic) nervous system (ANS):

A

nerves and ganglia (nerve cell bodies) outside the brain and spinal cord

122
Q

sympathetic nervous system (SNS):

A

excitatory component of ANS (accelerates heart rate, opens bronchial passages, dilates pupils, etc.); largely adrenergic (adrenaline, epinephrine)

123
Q

parasympathetic nervous system (PNS):

A

inhibitory component of ANS (decelerates heart rate, constricts pupils, aids in digestion); largely cholinergic (acetlycholine)

124
Q

somatic nervous system:

A

provides voluntary control over skeletal muscles; largely cholinergic

125
Q

enteric nervous system (ENS; not pictured):

A

controls function of the gastrointestinal tract; uses many transmitters, especially serotonin (5-HT) and dopamine (DA)

126
Q

DRUGS OF ABUSE ALTER FUNCTION OF ALL HUMAN ____ COMPONENTS

A

NERVOUS SYSTEM

127
Q

cell body (soma) of neuron:

A

includes nucleus (machinery for generating neurotransmitters and action potentials)

128
Q

axon of neuron:

A

conducts action potentials (electrical impulses) to synapse to release neurotransmitters

129
Q

dendrites:

A

receives signal from neurotransmitter release by pre-synaptic neuron

130
Q

synapses:

A

“space between” pre- and post-synaptic neurons that allows for inter-neuronal communication

131
Q

neurons have three major functions

A

inhibition

excitation

modulation

132
Q

neurons have three major functions—>inhibition:

A

reducing the likelihood of action potentials at post-synaptic neurons via release of inhibitory neurotransmitters

133
Q

neurons have three major functions—>excitation:

A

increasing the likelihood of action potentials at post-synaptic neurons via release of excitatory neurotransmitters

134
Q

neurons have three major functions—>modulation:

A

influencing neurotransmission of populations of neurons, usually through diffusion of neurotransmitters through tissue

135
Q

Describe six major steps of neurotransmission

A
  1. neurotransmitter synthesis
  2. neurotransmitter storage
  3. neurotransmitter release from the pre-synaptic terminal into the synapse
  4. neurotransmitter inactivation via removal of the synapse by reuptake or metabolism
  5. activation of the post-synaptic receptor
  6. signal transduction
136
Q

glial cells provide several functions that ___ neurotransmission

A

“support”

137
Q

oligodendrocytes:

A

synthesize myelin, thereby affecting neurotransmission speed via salutatory conduction whereby action potentials “jump” across nodes of Ranvier

138
Q

astrocytes:

A

form part of the blood-brain barrier; help guide neural migration (formation, maturation, function, and pruning of synapses) during circuit development; regulate neurotransmission and reuptake—especially for glutamate (an excitatory neurotransmitter implicated in addiction to certain substances)

139
Q

microglia:

A

immune-like cells that ordinarily do not cross the blood-brain barrier

140
Q

drug names: all drugs have at least three names:

A

chemical
generic (non proprietary)
trade (proprietary)

141
Q

drug classifications according to ___, and the major neurotransmitters they affect

A

psychotropic effects

142
Q

psychotropic means what?

A

=mind-altering

143
Q

drug classifications according to pharmacodynamic properties: stimulants

A

are dopamine (DA) agonists (↑ DA); they have arousing effects

144
Q

drug classifications according to pharmacodynamic properties: opioids

A

are opioid receptor agonists; they have primary analgesic (pain-relieving) and secondary sedative/anxiolytic (anti-anxiety) effects

145
Q

drug classifications according to pharmacodynamic properties: sedative hypnotics

A

indirectly elevate ϒ-aminobutyric acid (GABA); they have sedative/anxiolytic effects

146
Q

drug classifications according to pharmacodynamic properties: antidepressants

A

operate through several mechanisms, including DA, serotonin (5-HT) and norepinephrine (NE) agonism; they have mild mood elevating and mild anxiolytic effects

147
Q

drug classifications according to pharmacodynamic properties: psychedelics/hallucinogens

A

are direct or indirect serotonin (5-HT) agonists; they induce delusions, hallucinations, and paranoia

148
Q

drug classifications according to pharmacodynamic properties: antipsychotics

A

are dopamine D2 receptor and/or serotonin 5-HT2 receptor antagonists (↓ DA, 5-HT); they have calming/desensitizing effects

149
Q

absorption refers to

A

movement of a drug through the bloodstream, which is determined by several factors

150
Q

elimination refers to

A

processes through which drugs are removed from the body, including how they are metabolized by the liver and excreted in urine by the kidneys

151
Q

drug receptors are

A

“cellular elements…with which a drug interacts to produce its effect(s)”

152
Q

agonists are

A

drugs that bind to receptors (usually proteins on the surface of post-synaptic membranes) as if “turning them on with a key”

153
Q

antagonists are

A

drugs that bind to receptors (again, proteins on the surface of post-synaptic membranes) and block effects of agonists, like a “broken key that goes into a lock, cannot open the lock, and prevents other keys from opening the lock”

154
Q

others refer to agonists as any substance that___ (regardless of mechanism) and antagonists as any substance that ____ (regardless of mechanism)

A

increases neurotransmission

decrease neurotransmission

155
Q

dose-response functions

A

describe therapeutic (or other) effects of a drug over time at different amounts administered

156
Q

therapeutic ratio is

A

a means of indexing safety of a drug for a specific purpose

157
Q

Three Stages of Addiction

A
  1. binge/intoxication stage
  2. withdrawal/negative affect stage
  3. preoccupation/anticipation stage
158
Q

Three Stages of Addiction

1. binge/intoxication stage:

A 
reward (mesolimbic DA) and motor (nigrostriatal DA) systems implicated heavily
acute positive reinforcement effects predominate
liking emotions (pleasure, contentment, enthusiasm) are elicited
159
Q

Three Stages of Addiction

2. withdrawal/negative affect stage

A 
central nucleus of the amygdala and bed nucleus of the stria terminalis (BNST) implicated heavily (in addition to reward and motor systems)
acute punishment effects predominate
aversive emotions (disgust, fear, malaise) are elicited
160
Q

Three Stages of Addiction

3. preoccupation/anticipation stage

A 
prefrontal cortex, orbitofrontal cortex, and hippocampus implicated heavily (in addition to reward, motor, and punishment systems)
obsessive effects predominate
wanting emotions (craving, desire, preoccupation) are elicited
161
Q

Incentive Sensitization Theory

A

most influential theory of addiction over the last 20 years

very important because it accounts for emotional components of addiction, as reported by those who are addicted

when wanting and liking become decoupled, addiction ensues because individuals crave (want) the addictive substance even though they no longer derive pleasure from (like) using it

162
Q

motivation:

A

willingness to exert effort/perform work for a desired outcome

163
Q

primary reinforcers examples

A

(e.g., food, shelter, sex)

164
Q

secondary reinforcers examples

A

(e.g., money, achievement, prestige, drugs)

165
Q

in addiction, drugs of abuse take on ___ reinforcer properties

A

primary

166
Q

Drugs co-opt the evolutionarily old mesolimbic (midbrain) dopamine system (including the ventral striatum ) by activating it more___and more ___ than any primary reinforcer

A

intensely

enduringly

167
Q

active avoidance

A

willingness to exert effort/perform work to avoid punishment

168
Q

Both __ and __ play major roles in addiction

A

motivation

active avoidance

169
Q

animal models quantify motivation in several ways (3)

A
  1. amount of food or water consumed
  2. persistence of operant behaviors to obtain incentives
  3. intracranial self-stimulation (ICSS)
170
Q

How does amount of food or water consumed quantify motivation in animal models?

A

food deprived animals (e.g., 80% of ad lib body weight) eat more than non-food deprived animals

interpretation: food deprivation increases motivation to eat

171
Q

How does the persistence of operant behaviors to obtain incentives quantify motivation in animal models?

A

food deprived animals will work harder (e.g., lever-press, explore, swim) for food rewards than satiated animals

a history of higher doses of self-administered drugs of abuse increases rats’ breakpoints of responding on progressive ratio schedules of reinforcement

172
Q

breakpoint:

A

maximum number of operant responses (e.g., lever-presses) a trained animal will engage in for drug delivery

173
Q

classical conditioning:

A

repeatedly pairing two stimuli until the conditioned stimulus (CS) elicits the same response as the unconditioned stimulus (US)

174
Q

unconditioned stimulus:

A

a stimulus that elicits and unconditioned response

example: like all CNS stimulants, cocaine has laxative effects—an unconditioned response (UR) because it is reflexive

175
Q

conditioned stimulus:

A

a stimulus that, after repeated pairings with the US, elicits the UR

example: John picks up a small bag of crack from his drug dealer, places it in his pocket, and he immediately has to use the bathroom before consuming the drug

his body developed a conditioned response (CR ) to drug cues

176
Q

Why is Classical conditioning difficult to use as an index of motivation?

A

classical conditioning requires no work and is therefore difficult to use as an index of motivation

177
Q

operant conditioning:

A

changing the occurrence, frequency, or magnitude of behavior through use of reinforcement

learning stimulus-response contingencies

example: rats can be trained to engage in lever-pressing (an operant behavior) to self-administer cocaine (a secondary-turned-primary reinforcer)

178
Q

Why is operant conditioning better for motivation testing?

A

by definition, operant behaviors are motivated behaviors because they require effort/work

179
Q

intracranial self-stimulation (ICSS)

A

much of what we know about the neurobiology of motivation—and by extension addiction—began with foundational studies using intracranial self-stimulation ICSS

administration of short bursts (~250ms) of electrical activity directly into targeted neural structures

180
Q

c. drugs of abuse decrease ICSS thresholds meaning

A

(less electrical stimulation is needed for reinforcement)

181
Q

d. DA antagonists increase ICSS thresholds meaning

A

(more electrical stimulation is needed for reinforcement)

182
Q

different reinforcement schedules produce differential ___ of operant responding and differential ___ to extinction

A

persistence

resistance

183
Q

fixed vs. variable

predictable vs. unpredictable reinforcement

A

fixed ratio: reinforcement is delivered after a constant, or “fixed” number of correct behaviors (e.g., every 10th 20th, 30th, etc.)

variable ratio: reinforcement is delivered after unpredictable, or “variable” numbers of correct behaviors that average to a specific number (e.g., 10, 20, 30, etc.)

184
Q

interval vs. ratio

reinforcement is based on time vs. number of operant responses

A

fixed interval: reinforcement becomes available after a specific period of time (e.g., 30s, 60s, 120s)

variable interval: reinforcement becomes available after periods of time that are “variable”, but average to a specific interval (e.g., 30s, 60s, 120s)

185
Q

continuous vs. intermittent

A

continuous: reinforcement is delivered for every correct behavior

186
Q

Which schedule of reinforcement is the hardest to extinguish?

A

variable ratio schedules

this suggests greater motivation

187
Q

Which schedule of reinforcement is the easiest to extinguish?

A

continuous reinforcement schedules

188
Q

Animal model: intravenous drug self-administration

A

once addicted, animals will readily self-administer drugs intravenously by engaging in operant behaviors

this shows clear motivation to obtain drugs of abuse

some animals will self-administer cocaine until death, foregoing available food and water

189
Q

Animal model: oral drug self-administration

A

once addicted to alcohol, rats will choose water bottles with alcohol in them over bottles with only water

it is very difficult to get rats to start drinking alcohol

once addicted, they will drink up to 80 proof

many alcohol researchers now use vapor chambers

190
Q

Animal Model: changes to intracranial self-stimulation (ICSS) reward thresholds

A

administration of virtually all drugs of abuse decreases ICSS reward thresholds

less electrical stimulation is therefore needed for reinforcement (animals will work for less)

191
Q

Animal model: conditioned place preference

A

animals that receive drugs of abuse in a specific environment (place) will choose that environment during exploration while “sober”

this suggests desire (motivation) for the drug

this is why a lot of drug addicts die in hotels

192
Q

Animal model: drug taking despite aversive consequences

A

rats that have histories of 3 hours of access to cocaine per day decrease their drug-seeking behavior (lever-pressing) when foot-shocked

rats that have histories of 6 hours of access to cocaine per day do not change their drug-seeking behavior (lever-pressing) when foot-shocked

during withdrawal, addicted rats readily drink alcohol when quinine—which is very bitter—is added to their alcohol solution

193
Q

Animal Models of Withdrawal/Negative Affect (Stage 2 of Addiction): conditioned place aversion

A

administering naloxone (Narcan)—a powerful opioid antagonist—to opioid-dependent rats induces immediate withdrawal symptoms and conditioned place aversion

this place aversion can be induced in a single trial and is remarkably long-lasting

194
Q

Animal Models of Withdrawal/Negative Affect (Stage 2 of Addiction): anxious and fearful behaviors
(important: these are mediated by the amygdala and the hippocampus among other interconnected structures)

A

passive avoidance of novelty (e.g., less exploratory behavior in open fields and mazes)

important: active avoidance of aversive stimuli (e.g., mild shock) is very different and is mediated by the reward system

195
Q

Animal Models of Withdrawal/Negative Affect (Stage 2 of Addiction): increases in self-administration

A

rats given extended access to drugs of abuse increase their intake

196
Q

Animal Models of Preoccupation/Anticipation (Stage 3 of Addiction): drug-induced reinstatement

A

when non-contingent drug injections are administered (no operant response required), they reinstate extinguished responding at the same level that used to deliver the drug

197
Q

Animal Models of Preoccupation/Anticipation (Stage 3 of Addiction): cue-induced reinstatement

A

environmental cues that were previously paired with drug use (classical conditioning; see above), such as tones or lights, also reinstate lever pressing after prolonged periods of abstinence

198
Q

Animal Models of Preoccupation/Anticipation (Stage 3 of Addiction): stress-induced reinstatement

A

acute stress (e.g., intermittent foot shocks, food deprivation, restraint, tail pinches) reinstates cocaine-seeking behavior in rats and monkeys after prolonged abstinence

yohimbine administration (an α2-adrenergic receptor antagonist that activates the sympathetic nervous system

199
Q

Animal Models of Preoccupation/Anticipation (Stage 3 of Addiction): protracted abstinence

A

prior dependence lowers animals’ dependence thresholds

previously alcohol-dependent rats that are made re-dependent show more extreme withdrawal symptoms than those receiving alcohol for the first time

prior dependence induces alcohol/drug deprivation effects

previously dependent mice, rats, monkeys (and humans) show increased consumption of drugs and alcohol after a period of deprivation/abstinence

200
Q

direct sympathomimetics:

A

drugs that increase activity of the sympathetic nervous system (SNS) through direct action on adrenergic receptors

example: salbutamol: an adrenergic β2 receptor agonist used to treat asthma

many direct sympathomimetics have medical uses but few have abuse potential; we will not discuss them further

201
Q

indirect sympathomimetics:

A

drugs that mimic direct sympathomimetics by increasing availability of monoamines (DA, NE, 5-HT) in the synapse, which can occur through

(1) increased neurotransmitter release
(2) blocking neurotransmitter reuptake, and/or
(3) blocking neurotransmitter metabolism

202
Q

indirect sympathomimetics actions are complex, and occur through __ different DA receptors, __ families of NE receptors, and __ families of 5-HT receptors

A

5, 2, 7

203
Q

non-sympathomimetic stimulants:

A

drugs with stimulant properties that operate through other mechanisms

examples: caffeine blocks adenosine receptors (by binding to them); adenosine normally inhibits DA and glutamate activity

nicotine binds to acetylcholine receptors, and mimics actions of acetylcholine; it raises DA, glutamate, and gamma-aminobutyric acid (GABA) levels

204
Q

all CNS stimulants induce ___ arousal (an artificial F/F response)

A

sympathetic nervous system

205
Q

psychostimulant

A

(reward) effects are mediated by release of DA in the mesolimbic system (VTA, nucleus accumbens), regardless of the specific mechanism(s)

206
Q

locomotor

A

(motor activity) effects are meditated in large part through the nigrostriatal pathway

207
Q

Cocaine likelihood of addiction

A

(>20%) given any use in the past year

208
Q

What is freebase?

A

is a purified form of cocaine with a higher melting point than powered cocaine

powdered cocaine is mixed with ammonia, and freebase is extracted using ether, which, once evaporated, yields very pure cocaine crystals

209
Q

why is freebasing a problem?

A

because ether is highly flammable, freebasing is dangerous if not done carefully (and let’s face it, someone “jonesing” for a hit is not likely to be careful)

210
Q

Why is cocaine is highly dangerous?

A

because of both acute and long-term effects on the heart, vasculature, lungs, and kidneys

acute: increased heart rate, blood pressure,

increases in total peripheral resistance (TPR)

risk of heart attack

risk of stroke

permanent cardiac conduction abnormalities (e.g., right bundle branch block)

211
Q

Amphetamines: dextroamphetamine (D-amphetamine)

A

(brand names Dexedrine, Adderall) is still very popular to treat ADHD but has clear abuse potential

212
Q

methamphetamine

A

methylated derivative of amphetamine

synthesized from ephedrine (which has a similar chemical structure to amphetamine)

more potent because it crosses the blood-brain barrier more readily

213
Q

formication:

A

crawling sensation under the skin that leads to obsessive skin picking of the face and body–> found in methamphetamine use

214
Q

What are the half life(s) for methamphetamine and cocaine for behavioral effects?

A

6 hours for cocaine

12-16 hours for methamphetamine

215
Q

all stimulants exert their effects by increasing ___ of midbrain DA neurons

A

phasic neural firing

216
Q

amphetamine and cocaine administration increase ___ in both the mesolimbic and mesocortical DA systems, thereby altering neural structure directly

A

dendritic spine branching

217
Q

chronic cocaine and methamphetamine administration decrease ___ of mesolimbic DA neurons (see previous lecture notes (Links to an external site.)), a neural substrate of anhedonia, negative affectivity, and craving——->these changes are long-lasting

A

tonic neural firing

Psychology of Addiction (7 decks)

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