9/21 Addiction - Williams Flashcards Preview

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Flashcards in 9/21 Addiction - Williams Deck (22):
1

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 thinkingcontinued drug use may be due more to NEGATIVE reinforcement than positive rein

2

brain reward system

mesolimbic dopamine system

comprises:

  • ventral tegmental area (VTA)
  • nucleus accumbens (NAc)
  • projections to Medial Prefrontal Cortex

3

3 dopaminergic pathways

 

name - linked to?

nigrostriatal​ : Parkinson's disease

mesolimbic & mesocortical : addiction AND schizophrenia

tuberoinfundibular : diabetes insipidus (pituitary!)

4

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!

5

what substances are responsible for the high?

dopamine → dopamine receptors

endorphins → opiate receptors

6

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

 

7

animal models of drug addiction

1. conditioned place preference

  • animals learn to prefer drug-paired environment

2. drug self-administration

  • left unchecked, some animals will OD

3. relapse to drug self-admin

  • stimulated by drug OR drug-assoc cues/stress

4. intracranial self-stimulation

  • drugs promote animals choice to electrically stimulate brain reward regions

8

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

9

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

10

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

11

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

12

routes of drug admin

 

fastest?

why is oral not a huge concern?

  1. ingestion
    • oral methylphenidate DOESNT cause high DA release in NAc due to oral distribution
  2. inhalation → FASTEST
    • smoking is rapid route admin!
    • crack!
  3. injection
  4. snorting/snuffing
  5. through skin

13

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!

14

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

15

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

16

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

17

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

18

bigtime biological risk factor for addiction

psychiatric condition is one of the greatest risk factors (as many as 50%)

19

three stages of drug addiction

 

what is addiction???

1. binge → intoxication

2. withdrawal → negative affect

  • anything that makes you feel lousy
  • drives a lot of drug use behavior

3. 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)

20

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)

21

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!

22

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