Midterm 1 Flashcards
1
Q
Ways of Knowing intuition:
A
“I know it’s true because it makes sense (e.g., logic, street smarts)
2
Q
Ways of Knowing tenacity:
A
“I know it’s true because it’s always been that way”
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”
4
Q
Ways of Knowing science:
A
“It’s true insofar as measurable evidence from reliable instruments verify it repeatedly”
5
Q
DSM addiction categories focus exclusively on specific substances used and ____, with no consideration of ____
A
topographies of behavior, etiopathophysiology
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
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)
8
Q
What is the single most abused substance?
A
alcohol
9
Q
in recent years, ___ use has trended down, while ____ use has trended up
A
cocaine, prescription opioid
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
11
Q
in 2016, ___ was the leading cause of overdose in the US
A
fentanyl
12
Q
Heroin purity is unpredictable, and much stronger opiates ___ and ___ are sometimes cut in
A
fentanyl, carfentanil
13
Q
much of the vulnerability to SUDs (Substance Use Disorders) is ____
A
inherited
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
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)
16
Q
True or false: Genetic vulnerability alone cannot explain addiction
A
True
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
18
Q
Who stated that drug use was “Public Enemy Number 1”
A
President Richard Nixon in 1971
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
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
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
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
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
24
Q
Reagan cut what he called, “the spider’s web of welfare”, including (3)
A
- the Aid to Families with Dependent Children (AFDC) program (by 50%)
- the Supplemental Nutrition Assistance Program (food stamps), and
- Medicaid (all who lost AFDC funding lost Medicaid eligibility too)
25
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?
abolished parole in the federal prison system and established new, more strict federal sentencing guidelines
this lead to a huge spike in incarceration rates
26
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
$80 billion
| 10x more
27
Almost ___ are incarcerated for non-violent drug-related crimes, primarily ___
50%
| possession
28
1986 legislation signed by President Reagan that imposed federal ____ for drug offenses
mandatory minimum sentences
29
Blacks use drugs at ___ rate as Whites, but they are far more likely to be arrested and incarcerated
the same
30
Blacks comprise ___% of US drug users, but ___% of those arrested for drug violations, __% of those convicted, and __% of those sentenced to prison
15%
40%
60%
75%
31
Problems with disparities in mandatory sentencing (4)
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:
32
Is the war on drugs over?
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
33
Institutional racism
"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"
34
Direct racism:
policies that are purposefully designed to have discriminatory effects
EX: the original motivation for the war on drugs
35
Indirect racism:
practices that have disproportionate effects on people of different races without any intent to discriminate
36
An example of indirect racism
increased police presence in urban poor urban neighborhoods can result in more young Black males being arrested than Whites who commit similar crimes elsewhere
37
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)
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
38
addiction cannot be understood at any single level of analysis, neural, behavioral, emotional
neural:
sensitization of brain regions to drug cues (e.g., greater dopaminergic neural reactivity in the striatum); down-regulation of brain function via allostatic load
39
addiction cannot be understood at any single level of analysis, neural, behavioral, emotional
Behavioral:
use of larger amounts or over longer periods of time
40
addiction cannot be understood at any single level of analysis, neural, behavioral, emotional
emotional:
development of craving, a strong emotional urge to use
41
Neural Aspects of Addiction brain dopamine (DA) systems (3-4 depending on how they are parsed)
tuberoinfundibular pathway:
originates in the arcuate nucleus of the hypothalamus and projects to the pituitary gland; important for hormone regulation
42
Neural Aspects of Addiction brain dopamine (DA) systems (3-4 depending on how they are parsed)
nigrostriatal pathway:
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
43
Neural Aspects of Addiction brain dopamine (DA) systems (3-4 depending on how they are parsed)
mesolimbic pathway:
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)
44
Neural Aspects of Addiction brain dopamine (DA) systems (3-4 depending on how they are parsed)
mesocortical pathway:
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
45
Neural Aspects of Addiction--> brain dopamine (DA) systems (3-4 depending on how they are parsed) name them
tuberoinfundibular pathway, nigrostriatal pathway, mesolimbic pathway, mesocortical pathway
46
The brain dopamine (DA) systems that are subcortical (deep; "under" the cortex) and phylogenetically old
tuberoinfundibular pathway, nigrostriatal pathway, mesolimbic pathway,
47
The brain dopamine (DA) system mesocortical is (3)
1. largely cortical
2. is evolved fully in primates—particularly humans
3. provides top-down regulation over impulses generated by the subcortex
48
Dorsal/superior is which direction on the brain?
Top (see pic)
49
Rostral/anterior is which direction on the brain?
front
50
Ventral/inferior is which direction on the brain?
bottom
51
Caudal/posterior is which direction on the brain?
rear
52
The subcortex is linked to
motivation and emotion generation
53
The cortex is linked to
behavior and emotion regulation
54
tonic DA activity is associated with
mood states
55
high tonic DA →
positive affectivity (affective component of euphoria)
56
low tonic DA →
negative affectivity, irritability (affective components of craving)
57
mesolimbic DA activity is
experience dependent
58
repeated phasic activation produces
reduced tonic activity and sensitization
59
almost all drugs of abuse produce ___ in mesolimbic DA that (often far) exceed those induced by normal reinforces (e.g., food, sex):
phasic increases
60
note that neural firing propagates backward in time to ___ rather than substance delivery; this is also a major component of craving
cue exposure
61
thus, addiction is associated with (3)
1. reduced tonic neural firing, and
2. sensitized phasic neural firing, that
3. begins with cue exposure
62
allostatic load
recalibration of neural systems in response to repeated activation
63
reduced tonic neural activity may be induced by _____ or ____
```
adaptive recalibration of neural firing (e.g., via altered numbers of DA transporters and receptors)
long term (sometimes permanent) structural damage to DA neurons
```
64
Behavioral Aspects of Definitions: Koob, Arends, and Le Moal (2014) define addiction as: (3)
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
65
as discussed in Lecture 1, for many years drug use has been subdivided as follows: (3)
1. occasional, controlled, or social use
2. abuse
3. dependence/addiction
66
addiction is a ___ disease that is often characterized by ___
progressive, chronic relapsing
67
emotional and neural aspects of addiction cannot be disentangled fully, but they are not ____
isomorphic (Having a similar structure or appearance but being of different ancestry)
68
experience-dependent down-regulation of striatal DA activity produces ___ (3)
dysphoria
irritability
anhedonia (in some cases profound)
69
anhedonia
reduced motivation or ability to experience pleasure. one of the core features of depressions basically losing the ability to enjoy the things you love
70
The 2 Broad Types of "Genetics" Studies in Psychopathology Research, Including Addiction, are
Quantitative behavioral genetics
| Molecular genetics
71
Quantitative behavioral genetics (also called behavioral genetics, quantitative genetics, biometrical genetics):
objective: parse variance in behavior (trait, phenotype) into heritable (both genetic and non-genetic) and non-heritable (environmental) components, using latent variable modeling
72
this parsing of variance is accomplished using ___(3)
twin, family, and adoption studies
73
assumptions of a basic twin study:
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.)
74
ACE model:
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)
75
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 ___
reared together
| reared apart
76
trait-specific equal environments assumption:
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)
77
major limitation of ACE models:
do not account for GxE interactions or gene-environment correlations (rGE), which are unmeasured and subsumed within A2, resulting in overestimates of heritability
78
although peer influences account for initiation of alcohol use, heritability accounts almost entirely for ___ (2)
quantity and maintenance of use
79
Behavioral genetics tells us nothing about...
genes!
80
Molecular genetics:
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
81
polymorphisms (alleles, variants) are observed in only about ___% of our 30,000 protein-coding genes
1%
82
single base pair (SNP) =
single nucleotide polymorphism
83
genotype:
the specific gene(s) underlying a phenotype (see below), including addiction
84
phenotype:
observable characteristics (physical and/or behavioral) of an organism that may or may not correspond with a particular genotype
85
Mendelian inheritance (sometimes called dominance):
inheritance pattern for single-gene, dominant/recessive traits
86
Mendel's first law, also called the law of segregation, states that:
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.
87
very few human traits follow simple Mendelian inheritance patterns (4)
blood type
cystic fibrosis
Huntington's chorea
sickle-cell disease
88
human behavioral traits, including addiction, are inherited ___
multifactorially (via many genes)
89
DD and dd genotypes are ___
homozygotes
90
Dd and dD genotypes are ___
heterozygotes
91
important: in only 1 of 4 cases can we infer the ___ from the ___
genotype
| phenotype
92
no human behavior, and almost no psychiatric disorder, is determined by a ___
single gene
93
even traits that are influenced ____ by only a few genes carry unwieldy patterns of phenotypes
dominantly
94
trihybrid phenotype=
three-factor cross
95
Mendel's second law (the law of independent assortment)
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
polygenetic inheritance/determinism (sometimes called multifactorial inheritance):
the influence of multiple genes on a physical or behavioral phenotype
97
penetrance:
the proportion of individuals who carry genetic vulnerability (often called liability) and express the disorder
98
Example of penetrance
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
multifactorial inheritance:
like other psychiatric disorders, addiction is influenced by many genes, none of which are necessary or sufficient
100
In psychiatric molecular genetics, we usually use one of three approaches to identify candidate genes for different disorders, including addiction: (3)
genetic linkage studies, genetic association studies, genome-wide association studies (GWAS)
101
genetic linkage studies
genetic linkage refers to the tendency of alleles that are near one another on the same chromosome to be inherited together, or linked
102
In genetic linkage studies we...(4)
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
genetic linkage studies example
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
Problems with genetic linkage studies
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
genetic association studies
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
genetic association refers to situations in which
specific genes are associated with certain phenotypes
107
in association studies, we
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
genetic association studies problem
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
genome-wide association studies (GWAS)
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
gene polymorphism:
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
gene mutation:
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
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)
protein expression
transcription
translation
113
some genetically-derived individual differences in protein expression affect neurobiological processes such as ___in the brain, alcohol metabolism in the liver, etc
neurotransmission
114
polygenic determinism, or multifactorial inheritance
no single gene controls any complex human trait. Behaviors such as impulsivity, intelligence, and depression are affected by many genes. This is called
115
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
behavioral biases
116
genes affect neurotransmitter system function by (2)
altering neurotransmitter availability via synthesis and metabolism pathways
altering efficiency of neurotransmission more directly
117
MAO, COMT, DAT, and DRD4 genes are all implicated in ___ because they collectively alter DA function
impulsivity
118
higher levels of striatal DA are associated with ___, whereas lower levels are associated with ____
pleasure and contentment
| irritability and impulsivity
119
several candidate genes for alcohol and other substance dependencies are expressed in the ___, not the brain
liver
120
central nervous system (CNS):
brain and spinal cord
121
peripheral (autonomic) nervous system (ANS):
nerves and ganglia (nerve cell bodies) outside the brain and spinal cord
122
sympathetic nervous system (SNS):
excitatory component of ANS (accelerates heart rate, opens bronchial passages, dilates pupils, etc.); largely adrenergic (adrenaline, epinephrine)
123
parasympathetic nervous system (PNS):
inhibitory component of ANS (decelerates heart rate, constricts pupils, aids in digestion); largely cholinergic (acetlycholine)
124
somatic nervous system:
provides voluntary control over skeletal muscles; largely cholinergic
125
enteric nervous system (ENS; not pictured):
controls function of the gastrointestinal tract; uses many transmitters, especially serotonin (5-HT) and dopamine (DA)
126
DRUGS OF ABUSE ALTER FUNCTION OF ALL HUMAN ____ COMPONENTS
NERVOUS SYSTEM
127
cell body (soma) of neuron:
includes nucleus (machinery for generating neurotransmitters and action potentials)
128
axon of neuron:
conducts action potentials (electrical impulses) to synapse to release neurotransmitters
129
dendrites:
receives signal from neurotransmitter release by pre-synaptic neuron
130
synapses:
"space between" pre- and post-synaptic neurons that allows for inter-neuronal communication
131
neurons have three major functions
inhibition
excitation
modulation
132
neurons have three major functions--->inhibition:
reducing the likelihood of action potentials at post-synaptic neurons via release of inhibitory neurotransmitters
133
neurons have three major functions--->excitation:
increasing the likelihood of action potentials at post-synaptic neurons via release of excitatory neurotransmitters
134
neurons have three major functions--->modulation:
influencing neurotransmission of populations of neurons, usually through diffusion of neurotransmitters through tissue
135
Describe six major steps of neurotransmission
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
glial cells provide several functions that ___ neurotransmission
"support"
137
oligodendrocytes:
synthesize myelin, thereby affecting neurotransmission speed via salutatory conduction whereby action potentials "jump" across nodes of Ranvier
138
astrocytes:
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
microglia:
immune-like cells that ordinarily do not cross the blood-brain barrier
140
drug names: all drugs have at least three names:
chemical
generic (non proprietary)
trade (proprietary)
141
drug classifications according to ___, and the major neurotransmitters they affect
psychotropic effects
142
psychotropic means what?
=mind-altering
143
drug classifications according to pharmacodynamic properties: stimulants
are dopamine (DA) agonists (↑ DA); they have arousing effects
144
drug classifications according to pharmacodynamic properties: opioids
are opioid receptor agonists; they have primary analgesic (pain-relieving) and secondary sedative/anxiolytic (anti-anxiety) effects
145
drug classifications according to pharmacodynamic properties: sedative hypnotics
indirectly elevate ϒ-aminobutyric acid (GABA); they have sedative/anxiolytic effects
146
drug classifications according to pharmacodynamic properties: antidepressants
operate through several mechanisms, including DA, serotonin (5-HT) and norepinephrine (NE) agonism; they have mild mood elevating and mild anxiolytic effects
147
drug classifications according to pharmacodynamic properties: psychedelics/hallucinogens
are direct or indirect serotonin (5-HT) agonists; they induce delusions, hallucinations, and paranoia
148
drug classifications according to pharmacodynamic properties: antipsychotics
are dopamine D2 receptor and/or serotonin 5-HT2 receptor antagonists (↓ DA, 5-HT); they have calming/desensitizing effects
149
absorption refers to
movement of a drug through the bloodstream, which is determined by several factors
150
elimination refers to
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
drug receptors are
"cellular elements...with which a drug interacts to produce its effect(s)"
152
agonists are
drugs that bind to receptors (usually proteins on the surface of post-synaptic membranes) as if "turning them on with a key"
153
antagonists are
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
others refer to agonists as any substance that___ (regardless of mechanism) and antagonists as any substance that ____ (regardless of mechanism)
increases neurotransmission
| decrease neurotransmission
155
dose-response functions
describe therapeutic (or other) effects of a drug over time at different amounts administered
156
therapeutic ratio is
a means of indexing safety of a drug for a specific purpose
157
Three Stages of Addiction
1. binge/intoxication stage
2. withdrawal/negative affect stage
3. preoccupation/anticipation stage
158
Three Stages of Addiction
| 1. binge/intoxication stage:
```
reward (mesolimbic DA) and motor (nigrostriatal DA) systems implicated heavily
acute positive reinforcement effects predominate
liking emotions (pleasure, contentment, enthusiasm) are elicited
```
159
Three Stages of Addiction
| 2. withdrawal/negative affect stage
```
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
Three Stages of Addiction
| 3. preoccupation/anticipation stage
```
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
Incentive Sensitization Theory
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
motivation:
willingness to exert effort/perform work for a desired outcome
163
primary reinforcers examples
(e.g., food, shelter, sex)
164
secondary reinforcers examples
(e.g., money, achievement, prestige, drugs)
165
in addiction, drugs of abuse take on ___ reinforcer properties
primary
166
Drugs co-opt the evolutionarily old mesolimbic (midbrain) dopamine system (including the ventral striatum ) by activating it more___and more ___ than any primary reinforcer
intensely
| enduringly
167
active avoidance
willingness to exert effort/perform work to avoid punishment
168
Both __ and __ play major roles in addiction
motivation
| active avoidance
169
animal models quantify motivation in several ways (3)
1. amount of food or water consumed
2. persistence of operant behaviors to obtain incentives
3. intracranial self-stimulation (ICSS)
170
How does amount of food or water consumed quantify motivation in animal models?
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
How does the persistence of operant behaviors to obtain incentives quantify motivation in animal models?
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
breakpoint:
maximum number of operant responses (e.g., lever-presses) a trained animal will engage in for drug delivery
173
classical conditioning:
repeatedly pairing two stimuli until the conditioned stimulus (CS) elicits the same response as the unconditioned stimulus (US)
174
unconditioned stimulus:
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
conditioned stimulus:
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
Why is Classical conditioning difficult to use as an index of motivation?
classical conditioning requires no work and is therefore difficult to use as an index of motivation
177
operant conditioning:
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
Why is operant conditioning better for motivation testing?
by definition, operant behaviors are motivated behaviors because they require effort/work
179
intracranial self-stimulation (ICSS)
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
c. drugs of abuse decrease ICSS thresholds meaning
(less electrical stimulation is needed for reinforcement)
181
d. DA antagonists increase ICSS thresholds meaning
(more electrical stimulation is needed for reinforcement)
182
different reinforcement schedules produce differential ___ of operant responding and differential ___ to extinction
persistence
| resistance
183
fixed vs. variable
| predictable vs. unpredictable reinforcement
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.)
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interval vs. ratio
| reinforcement is based on time vs. number of operant responses
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)
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continuous vs. intermittent
continuous: reinforcement is delivered for every correct behavior
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Which schedule of reinforcement is the hardest to extinguish?
variable ratio schedules
| this suggests greater motivation
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Which schedule of reinforcement is the easiest to extinguish?
continuous reinforcement schedules
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Animal model: intravenous drug self-administration
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
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Animal model: oral drug self-administration
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
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Animal Model: changes to intracranial self-stimulation (ICSS) reward thresholds
administration of virtually all drugs of abuse decreases ICSS reward thresholds
less electrical stimulation is therefore needed for reinforcement (animals will work for less)
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Animal model: conditioned place preference
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
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Animal model: drug taking despite aversive consequences
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
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Animal Models of Withdrawal/Negative Affect (Stage 2 of Addiction): conditioned place aversion
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
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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)
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
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Animal Models of Withdrawal/Negative Affect (Stage 2 of Addiction): increases in self-administration
rats given extended access to drugs of abuse increase their intake
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Animal Models of Preoccupation/Anticipation (Stage 3 of Addiction): drug-induced reinstatement
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
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Animal Models of Preoccupation/Anticipation (Stage 3 of Addiction): cue-induced reinstatement
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
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Animal Models of Preoccupation/Anticipation (Stage 3 of Addiction): stress-induced reinstatement
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
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Animal Models of Preoccupation/Anticipation (Stage 3 of Addiction): protracted abstinence
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
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direct sympathomimetics:
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
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indirect sympathomimetics:
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
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indirect sympathomimetics actions are complex, and occur through __ different DA receptors, __ families of NE receptors, and __ families of 5-HT receptors
5, 2, 7
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non-sympathomimetic stimulants:
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
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all CNS stimulants induce ___ arousal (an artificial F/F response)
sympathetic nervous system
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psychostimulant
(reward) effects are mediated by release of DA in the mesolimbic system (VTA, nucleus accumbens), regardless of the specific mechanism(s)
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locomotor
(motor activity) effects are meditated in large part through the nigrostriatal pathway
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Cocaine likelihood of addiction
(>20%) given any use in the past year
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What is freebase?
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
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why is freebasing a problem?
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)
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Why is cocaine is highly dangerous?
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)
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Amphetamines: dextroamphetamine (D-amphetamine)
(brand names Dexedrine, Adderall) is still very popular to treat ADHD but has clear abuse potential
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methamphetamine
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
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formication:
crawling sensation under the skin that leads to obsessive skin picking of the face and body--> found in methamphetamine use
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What are the half life(s) for methamphetamine and cocaine for behavioral effects?
6 hours for cocaine
12-16 hours for methamphetamine
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all stimulants exert their effects by increasing ___ of midbrain DA neurons
phasic neural firing
216
amphetamine and cocaine administration increase ___ in both the mesolimbic and mesocortical DA systems, thereby altering neural structure directly
dendritic spine branching
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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
tonic neural firing
