Lecture 8: Pharmacology of Drugs of Abuse Flashcards
3 ways drugs are classified into schedules
- medical use
- abuse potential
- likelihood of dependence when abused
Requirements for schedule I
- no accepted medical use
- lack of accepted safety under medical supervision
- high potential for abuse
requirements for schedule II
substances with high potential for abuse, which may lead to severe psychological or physical dependence
requirements for schedule III
less potential for abuse and may have moderate or low physical dependence or high psychological dependence. includes codeine, ketamine, suboxone
requirements for schedule IV
low potential for abuse e.g. xanax
requirements for schedule V
low potential for abuse and primarily containing limited quantities of certain opiates
estimated cost of drug use to society in lost productivity, health care expense, and crime-related and other costs exceeds ___
half a trillion dollars annually
drug use is highest among people in their ___
late teens and twenties
drug use is ___ among people in their fifties
increasing
abuse of prescription stimulants is ____
increasing
nosology
classification of diseases
differences in DSM5 SUD
diagnose people by looking at continuum of severity, + dual diagnosis
who discovered the reward circuit in the brain?
olds and milner in 1950s
rats preferred ___ to ____
intracranial self stimulation (ICSS) to other natural reinforcements
drugs hijack normal mechanisms underlying ___
reinforcement learning
5 areas drug abuse acts on
- VTA
- nucleus accumbens
- hippocampus
- amygdala
- prefrontal cortex
what do VTA and NA mediate?
acute pleasurable sensation
hippocampus and amygdala are responsible for ___
memories of pleasure
PFC impairments mediate ___
long term changes involved in loss of control, relapse
pathway of drug reinforcement (starts with, +4)
VTA
- amygdala
- nucleus accumbens
- PFC
- ACC
Nora Volkow discovered ___
significant relationship between intensity and duration of rush with cocaine and degree to which drug blocks dopamine reuptake
DA release is related to the size of a ____, which controls ____
- prediction error
2. error-driven learning
error can be conceived either as the difference between ___ or difference between ____
- correct and actual response
2. predicted and actual outcome
DA release is relatd to the error term in ___
temporal-difference learning
when something good happens that is unexpected, ___
more dopamine is released than if the good thing was expected
4 variables making someone prone to addiction
- stress
- genetic background
- environment
- social context
___ is profoundly altered by chronic drug abuse. how?
frontal lobe; lower metabolic rate in frontal lobe
____ occurs after long term drug abuse
cortical hypofrontality; decreased cerebral blood
fewer dopamine receptors appear in ____
NAc; homeostatic down regulation
frontal lobes become ___ to drug-related stimuli
sensitized
over time, ____ produce a greater response in reward pathway than rewarding stimuli themselves
stimuli that predict drugs
9 structures involved in addiction
- frontal cortex
- prefrontal cortex
- parietal cortex
- OFC
- VTA
- basal ganglia
- nucleus accumbens
- amygdala
- hippocampus
3 major conditions that trigger relapse
- reexperience with drug
- conditioned drug cues
- stress
6 structures involved in glutamatergic addiction
- medial prefrontal cortex
- OFC
- anterior cingulate cortex
- thalamus
- hippocampus
- amygdala
main role of glutamate in addiction
release glu into NAc and VTA; craving mediated as increased glu activity within reward circuit
____ protein accumulates in ___ after chronic use of drugs
delta FosB
NAc
several drugs of abuse also reduce ____
neurogenesis
what parts are involved in signaling significance or desirability of stimulus in motivational circuits? (2)
- NAc
2. amygdala
what part provides incentive for obtaining reward in conditioning/learning pathways?
hippocampus
what part strengthens behaviors that obtain reward and weaken inhibitory processes?
frontal lobe
how high is the heritability of addiction?
0.3-0.7
chromatin (2 components)
histones and DNA
histones
spools of protein around which strands of DNA are wound; thin tail extends
charge of histones and effect
positive; helps attract negatively charged DNA
nucleosome
eight histones plus 166 base pairs of DNA
DNA methylation
adds methyl group to DNA; alters expression of genes by activating or repressing
epigenetic factors; where they bind and what they effect
biochemical molecules that bind to histone tails; affect how tightly DNA molecule is wound around histones
DNA that is loosely bound is ___, DNA tightly wound is ____
easily activated
not easily activated
5 biochemical mechanisms of epigenetic process
- methylation
- acetylation
- phosphorylation
- ubiquitination
- sumoylation
when histones are tightly compacted, genes on DNA are ___
hidden within nucleosome and not easily exposed
to turn genes on and off, the structure of ___ has to be altered
chromatin
DNA methylation ___, whereas demethylation ___
- silences genes
2. opposite effect
histone acetylation ___, whereas histone deacetylation ____
enhances gene transcription
opposite effect
enzyme involved in methylation
DNA methyltransferase, DNMT
enzyme involved in demethylation
DNA demethylase
enzyme involved in histone acetylation
histone acetyltransferase, HAT
DNA methylation can lead to ___
histone deacetylation
drugs of abuse cause changes in ___
histone acetylation
expression of ___ is under epigenetic control
expression of delta FosB; makes it more responsive on subsequent reexposure to drug
3 methods of pharmacotherapy for SUD
- agonist substitution
- partial agonist substitution
- antagonists
opioid addiction agonist
methadone
nicotine addiction agonist
nicotine lozenges, gum, patches
alcohol addiction agonist
antabuse (disulfiram); acetaldehyde buildup
partial agonist for opioids
buprenorphine
partial agonist for nicotine
varenicline
3 opiate antagonists
- naloxone
- naltrexone
- nalmefene
GABA-__ agonists, like ___, can reduce reinforcing effects of drugs
B; baclofen; anticonvulsants
there are ___ on GABA neurons in VTA, and their activation ___. what can have similar effect?
mu opioid receptors; disinhibits DA neurons
CB1 receptors
kappa receptor stimulation ___ and can result in ___
reduces activity in NAc; leads to dysphoria
what makes naltrexone effective?
blocks actions of endorphins released by alcohol and mediate pleasure; very high affinity antagonist of mu opioid receptor
how can vaccines help with relapse prevention?
- stimulate production of drug specific antibodies
antibodies bind to drug molecules and keep them from crossing BBB
