9/21 Addiction - Williams Flashcards
simple terms: why do people use and abuse drugs?
1. high as a reward
- reward: pos emotional effect
2. positive reinforcement
- behavioral response to maintain/increase a stimulus that elicits a good/pos effect
3. negative reinforcement
- behavioral response to a stimulus that elicits avoidance of stimuli that feel bad/negative
current thinking: continued drug use may be due more to NEGATIVE reinforcement than positive rein
brain reward system
mesolimbic dopamine system
comprises:
- ventral tegmental area (VTA)
- nucleus accumbens (NAc)
- projections to Medial Prefrontal Cortex
3 dopaminergic pathways
name - linked to?
nigrostriatal : Parkinson’s disease
mesolimbic & mesocortical : addiction AND schizophrenia
tuberoinfundibular : diabetes insipidus (pituitary!)
biology of addiction:
DOPAMINE
DA resp for reinforcing pleasureable effects of drugs/alcohol
- addictive substances cause release of DA in NAc (shell) → pleasure/high
diff drugs enter into the system at different places, but virtually all activate the reward pathway in some way!
what substances are responsible for the high?
dopamine → dopamine receptors
endorphins → opiate receptors
brains are “hard wired” for addiction
why do we say that?
why might this be?
evidence: human brains, rat brains all have the areas that make up the addiction pathway (VTA, NAc, PFC)
- ventral tegmental area
- nucleus accumbens
- prefrontal cortex
reward pathways in nature respond to PLEASURE and maintain the species
- food
- water
- sex
- nurturing
animal models of drug addiction
- conditioned place preference
* animals learn to prefer drug-paired environment - drug self-administration
* left unchecked, some animals will OD - relapse to drug self-admin
* stimulated by drug OR drug-assoc cues/stress - intracranial self-stimulation
* drugs promote animals choice to electrically stimulate brain reward regions
conditioned place preference
obj: study rewarding/aversive effects of drugs
- tests time spent in drug-paired space
- cocaine: conditioned place pref
- lithium: conditioned place aversion
self administration
obj: assess rewarding properties of drug
- if animals actively work at behavioral task to receive a dose of the drug, likely that drug will be rewarding in humans too
- non-addicting drugs → no effect on DA conc in reward pathways → no self-admin
- addicting drugs → YES effect on DA conc in reward pathways → YES self-admin
categories of addictiveness
Controlled Substances Act
Schedule I
- high potential for abuse
- no medical use
- MDMA, heroin, GHB, marijuana, LSD
Schedule II
- high potential for abuse
- medical use
- cocaine, PCP methylphenidate (ritalin), methamphetamine
Schedule III
- lower potential for abuse
- rohypnol, ketamine, codeine, dronabinol
Schedule IV
- low potential for abuse
- benzodiazepines, zolpidem
Schedule V
- low potential for abuse
- codeine cough med
intracranial self-stimulation
probe placed in a place in which electrical stim duplicates stim of reward pathway
- animal will attempt to self stim as quickly/as much as possible
human version: pt B19 with electrode in medial forebrain bundle → overwhelming euphoria
routes of drug admin
fastest?
why is oral not a huge concern?
- ingestion
- oral methylphenidate DOESNT cause high DA release in NAc due to oral distribution
- inhalation → FASTEST
- smoking is rapid route admin!
- crack!
- injection
- snorting/snuffing
- through skin
why can we give some addictive drugs orally (vs. IV)
greater DA release → greater high
implication: routes of admin that DONT result in v high DA release will be less addictive
- greater abuse potential for IV drugs vs oral drugs
- oral stimulants can be taken more safely/less addictive potential-y than parenteral admin!
how does cocaine cause such a tremendous high?
potentiates its own high!
- activates reward pathway → leads to release of DA from presynaptic cell
- blocks DA reuptake pump! → leads to higher conc of DA in synaptic cleft
why do some become addicted while others do not?
biological factors → 50% due to heritability
- compare to heritability of chronic medical illness…
- HTN 35%
- DM1 40%, DM2 80%
- asthma 55%
- substance use disorder
- heroin 35%
- alcohol 55%
- marijuana 50%
- concl: not v diff heritability than chronic conds
environmental factors
- stress
- early physical/sexual abuse
- witnessing violence
- peers who use
- drug availability
old theory of DA vs new understanding
old theory: substance users have
- increased sensitivity to DA
- higher levels of DA in brain
THIS IS FALSE.
new understanding: pt with SUD have
- lower DA concentration
- reduced reinforcement responses
evidence: hit controls and detoxed cocaine abusers with methylphenidate and see decreased DA increases, reduced reinforcing responses to MP
4 circuits involved in drug abuse/addiction
memory/learning
- amygdala
- hippocampus
reward/salience
- NAc
- VP: ventral pallidum
motivation/drive
- OFC: orbitofrontal cortex
- SCC: subcallocal cingulate cortex?
inhibitory control
- prefrontal cortex
- ACG: anterior cingulate cortex
bigtime biological risk factor for addiction
psychiatric condition is one of the greatest risk factors (as many as 50%)
three stages of drug addiction
what is addiction???
- binge → intoxication
- withdrawal → negative affect
- anything that makes you feel lousy
- drives a lot of drug use behavior
- preoccupation → anticipation/craving
addiction is a combination of reward deficit + excess stress
- newer thinking focus on negative reinforcement, effect of negative affect
- using occurs not just to achieve the high, but to take the edge off of the lousier elements of one’s life (stress)
recovery
POSSIBLE
bc it’s a brain disorder!
scans of brains further along in post-addiction timeline show significant “recovery” (moving closer to normal brain)
gambling disorder
persistent/recurrent problematic gambling
1% of pop, more in males
heritable
linked to: anxiety, depression, SUD, personality disorder
4 or more of the following in 12 months:
- needing to gamble with more money (tolerance)
- restless/irritable when trying to cut/stop
- unsuccessful efforts to stop
- preoccupied with gambling
- gambling when distressed
- after losing, gamble more to “chase loss”
- lies to conceal extent of gambling
- lost job/school/relationship form gambling
- financial issues
show same brain signs as addiction! more nucleus accumbens activity during anticipation of
- LARGE vs small reward
- reward vs no outcome
also show decreased activity in anterior cingulate (inhibition/impulse control!
