The Cognitive Neuroscience of Addiction Flashcards
1
Q
SUBSTANCE USE REASONING
A
- psychoactive drugs used for various reasons:
1 . ALCOHOL = relaxing/enhancing social experiences/anxiety & depression reduction
2. COFFEE = to wake up
3. NICOTINE = experience/stimulant/social reasons
4. MDMA = improve social experience
5. COCAINE = confidence/enhance social experience/work focus
6. HEROINE = relax/belonging/safety
2
Q
ADDICTION
A
- 6% alcohol users meet alcohol disorder criteria
- addicts experience intense cravings for desired substances/severe withdrawal symptoms w/o it
- addicts oft go to extreme lengths to obtain drug; profound effect on physical/mental health -> potentially devastating effect on families/work/education/social life
- degrees of withdrawal dif between people/drugs
3
Q
ADDICTION DRUGS
A
DRUGS ASSOCIATED W/ADDICTION - nicotine - alcohol - amphetamine - caffeine - heroine - cocaine/crack - prescription drugs (ie. painkillers/Benzo's) LESS ASSOCIATED - MDMA - psychedelics ASSOCIATED BEH - gambling - gaming
4
Q
COCAINE
A
- addiction associated w/brain damage risk number appearing m-h post consumption incl. YA stroke (early 30s)/seizures
- lesions = movement disorders
- subtle pathology = reduced volume of inferior portion of frontal lobe
5
Q
HEROIN
A
- associated w/broad pathology range incl. grey matter reduction; brain hypoxia (reduced oxygen availability); cerebral edema (water saturation); stroke (blood supply loss); spongiform leukoencephalopathy (gen white matter axon loss); myelopathy (paralysis via spinal lesions)
- frontal/temporal regions = reduced grey matter density in heroin-dependents; correlation between grey matter density reduction associated w/longer heroin use
6
Q
ALCOHOL
A
- alcoholism linked strongly w/Wernicke-Korsakoff syndrome
- Wernicke encephalopathy = gen brain shrinkage
- Korsakoff syndrome = chronic Wernicke “end-stage”; psychiatric diagnosis characterised by anterograde amnesia (inability to remember new things); sometimes treated w/thiamine supplements; associated w/enlarged ventricles/cortical sulci; indicates brain tissue loss
7
Q
CANNABIS
A
YUCEL et al (2008)
- carefully selected long-term (>10y) heavy (>5 joints daily) cannabis using men w/19.7y on average w/o other neurologic/mental health complications
- pps contrasted w/16 controls
- user brain volume reduced in hippocampus/amygdala
8
Q
CANNABIS X PSYCHOSIS
A
MOORE et al (2007)
- way of testing if drug use -> mental illness = large scale longitudinal research assessing psychiatric youth status prior to drug use then again in adulthood post cannabis use
- odd ratios = increased psychosis diagnosis risk in heavy cannabis users VS others; doubling psychotic symptoms risk (ie. schizophrenia) in heavy cannabis
9
Q
ADDICATION CAUSES
A
- vast research done around it
- large inter-individual variability in addiction susceptibility
- 10-20% regular drug abusers = addicted; specific stats vary on drug
- similar estimates drawn from animal addiction models research; similar percentage in animals systematically administered potent drugs preferring drugs > sucrose
- genetic addiction attribution estimate = 50%
10
Q
LEARNING PERSPECTIVE OF RELAPSE
A
- associative learning addiction theories construe drug taking = conditioning
- instrumental conditioning paradigm = drug as reinforcer; strengthens drug-related cues/drug use associations
- ie. friends who smoke -> smoking -> nicotine euphoria
11
Q
LEARNING EXPLANATION OF RELAPSE
A
- stopping ie. smoking starts process of extinction-reducing association strength between various smoking cues/smoking ie. potent cues removed from equation BUT not extinguished
- context-driven relapse = cue re-exposure elicits conditioned response aka. smoking
- extinction procedures involving multiple cue exposure w/o reward = effective as potency reduction via relapse trigger BUT difficult pull off
- research suggests extinction treatments limited to rehab centres = less effective/long-term < treatments in equivalent contexts similar to addiction development (ie. addicts home)
12
Q
“WE ARE W/O DEFENCE AGAINST THE FIRST DRINK”
A
- first dose potential to produce enhanced craving = extensively documented; common to all drug abuse
- reasoning could incl. sensory experiences associated w/drug use (ie. tobacco smell) = strong cues alone
- if someone stops smoking extinction hasn’t affected cues; first re-exposure may elicit strong conditioned response (ie. smoking)
- cue relativity clearly detected in addict brain activity
13
Q
CCR (CONDITIONED COMPENSATORY RESPONSE)
A
SUBKOV & ZILOV (1937)
- Pavlov’s colleagues
- injected dogs w/adrenaline (epinephrine) severally
- raising blood adrenaline effect -> ^HR
- ^HR following each injection got constantly smaller
- dogs developed adrenaline tolerance
- aka. organism compensates for adrenaline effect via HR reduction around injection time
14
Q
CCR +
A
- to explore whether compensatory reaction actually required drug, researchers placed dogs in same stand; injected w/placebo (neutral substance ineffective on blood adrenaline)
- researchers observed substantial HR decrease following placebo injection
- dogs conditioned to reduce HR as injection-related context response
- following acquisition, compensatory response didn’t require drug -> it was conditioned compensatory response
- SO drug effect = US; cues associated w/administration = stimuli
15
Q
CCR: HEROIN
A
SIEGEL et al (1982)
- injected 3 rat groups w/large heroin dose
- group 1 = previously tested on small dose; same settings (same-tested c)
- group 2 = previously tested on small dose; dif cage (dif-tested c)
- group 3 = heroin-naive (first time tested c)
- fatality overdose = 1 -> 2 -> 3
16
Q
OVERDOSE
A
- heroin suppresses CNS activity
- incl. other strong effects ie. reduced HR/respiration/BP -> organism learned compensation via ^HR/BP aka. conditioned compensatory response
- response absence = stronger drug effect aka. overdose potential
- new environment + heroin use = removed CS eliciting conditioned compensatory response -> morphine effect (lowered HR/BP) = stronger -> heroin overdose
17
Q
OVERDOSE +
A
HEROIN
- heroin overdose victims = seldom novices SO repeated use -> conditioned compensatory response
- oft overdose cases involve some significant drug use context change (ie. rock-star overdoses in unfamiliar hotel/city)
ALCOHOL
- alcohol = stronger effect in exotic drinks/cocktails > familiar drinks as taste change reduces CCR
- one gets drunker easier in unfamiliar company > old friends as company change reduces CCR
18
Q
TOLERANCE
A
- CCR = tolerance form to drug effects
- tolerance effects = complex
- homeostatic protection form reduces potentially harmful drug effects
- tolerance -> overdose (sometimes) if necessary conditions (ie. contextual cues) = absent
- tolerance in dose ^; constantly larger doses required for desired effect
- “ironic” = homeostatic protection mechanisms underlying tolerance increase addictive potential as physiological mechanisms underlying tolerance contribute to withdrawal symptoms
19
Q
CCR: ALCOHOL
A
- alcohol tolerance based on GABA receptor desensitisation where alcohol = agonist
- above = protective role in alcohol consumption BUT when consumption ceases -> brain excitation/inhibition imbalance -> psychological/motor agitation characteristic of alcohol withdrawal
- brain always wants equilibrium SO…
drug pushes X up -> brain tries to push X down -> takes a while for it to stop pushing
20
Q
TOLERANCE X WITHDRAWAL
A
- heroin reduces HR/BP
- users = tolerance via raising BP/HR
- discontinued drug -> abnormally ^ BP/HR (+ insomnia/other CNS hyperactivity)
- withdrawal symptoms caused via prior adjustments in nervous system to combat drug effects w/o it there -> craving rise/motivational state like hunger; adapted system will seek drug
- avoiding withdrawal/craving = primary factor promoting addiction
21
Q
DRUGS = REWARDS
A
- drug-related cues/withdrawal avoidance explain some addictive potential BUT don’t capture whole picture ie. don’t explain why someone who quit long ago/doesn’t severely withdraw/not exposed to drug-related cues STILL may relapse
- conditioning-based addiction models find it hard to account for abuse drugs ^ desired w/use (unlike natural reinforcers ie. food/sex)
- cue activity/withdrawal models limits + dopaminergic circuits discovery + their importance in natural rewarding stimuli processing = abuse drugs are addictive due to exceptional reward
22
Q
UNIVERSAL REINFORCEMENT CIRCUIT
A
- studies employing electric stimulation in rats = animals prepared for hard work (ie. lever pressing) to receive VTA/nucleus accumbens stimulation
- humans = PET/fMRI studies show reinforcer variety presentation (ie. juice/money/sex/alcohol/humour) -> ^ basal ganglia (esp. nucleus accumbens) activation
- other research = rats; encounters w/natural reinforcers (ie. food/sex) -> dopamine release from VTA neurons in synapses w/nucleus accumbens
23
Q
DOPAMINE X REINFORCEMENT
A
WISE et al (1978)
- rats trained to press lever for food
- post training split into 3 groups
- group 1 = lever pressing still reinforced via food
- group 2 = lever pressing no longer reinforced; gradually stopped pressing
- group 3 = given dopamine antagonist pimozide; reinforcement continued
- despite same reinforcer presence, group 3 rats = same lever pressing reduction as w/o reinforcement
24
Q
ANHEDONIA HYPOTHESIS
A
- dopamine = happiness chemical
- dopaminergic synapses covey “goodness” (ie. food = goodness)
- dopamine antagonists ie. pimozide reduce effect thus reducing animal’s propensity to work for food
- BUT evidence soon contradicted this
25
Q
DOPAMINE X ADDICTION
A
- LT users (esp drugs affecting dopamine transmission ie. cocaine/amphetamines); less usage euphoria over time
- regular users = reduction in drug “high”
- BUT drug craving does NOT decrease but ^
- apparent disconnection between liking/wanting
- animal studies; dopaminergic synapses (esp. nucleus accumbens) primarily processing incentive (motivational) > hedonic (euphoria-related) stimuli value; drugs modulating dopamine influence motivation > euphoria
26
Q
DOPAMINE = WORK MOTIVATOR
A
- 2 rat groups trained to press lever for sugar/alt pellets
- 1 group = nucleus accumben dopamine synapses disrupted; experimenters compared food pref/lever processing post training
- both groups preferred sugar to less tasty alternative when both free
- BUT w/lever pressing, only healthy rats wanted to work while impaired dopamine transmission rats happy to settle for alt
27
Q
INCENTIVE SALIENCE THEORY
A
- alternative to anhedonia hypothesis
- dopaminergic circuit w/NA/VTA isn’t responsible for pleasure obtained from drug BUT for obtaining motivation
- doesn’t dispute that euphoria induced via abuse drugs contributes to consumption OR cue reactivity importance/withdrawal avoidance in eliciting/maintaining drug use
- BUT claim above factors aren’t sufficient to explain addiction in LT users; relapse post therapy
- addicts sensitised to drugs (ie. heroin/cocaine/alcohol/amphetamine) as use strongly affects motivation-related dopaminergic relapses in brain
- repeated drug use -> greater dopamine circuit responses independently from drug effects on euphoria
28
Q
MOTIVATIONAL STATE EFFECTS
A
- paying people not to use helps
- pregnant women find it easier not to smoke
- other options other than use helps
29
Q
COMORBIDITY
A
- drug/alcohol diagnosis probability dependence ^ w/mental illness severity (incl. mood (ie. depression)/anxiety (ie panic disorder)/eating disorder/intermittent explosive disorder/psychotic symptoms (schizophrenia))
30
Q
CAUSE -> EFFECT
A
- comorbidity between drug dependence/mental illness does NOT clarify causality direction:
1. drug use could use mental illness via neurotoxicity
2. mental illness could cause drug dependence via self-medication
3. both causal mechanisms might exist/be reciprocated
31
Q
DRUGS -> MENTAL ILLNESS
A
- drugs associated w/^ neuropathology risk
- substantial evidence that drug use causes mental illness (look back at cannabis/psychosis)
32
Q
EXPERIMENTAL INDUCTION PROCEDURES
A
MCKEE et al (2011)
- pps described most stressful even in past 6m; scripted by clinician; recorded as audio; later played back to pps
- another session; received neutral script created similarly; completed abstinence incentive task; could some in next 50m BUT would earn money p/5m abstinence
- smoked ad libitum to determine how much they smoke/enjoy smoking
- stress decreased delay to initiate smoking in abstinence incentive task
- smoking = more rewarding
33
Q
SELF-MEDICATION ROLE
A
- in addition to cue reactivity/tolerance/reward circuit disruption), self-medication proposed
- addicts gen suffer from co-morbidities (psychiatric/psych disorders ie. anxiety/depression/schizophrenia)
- oft regarded as vulnerability factors/addiction consequences previously
- increasing recognition of addicts using drugs to alleviate mental illness symptoms; “self-medication” need = key factor leading to/maintaining addiction
34
Q
SUMMARY
A
- drug addiction unlikely explained via single factor
- 4 factor contribution discussed today extensively documented
- still debated regarding mechanisms abnormal in addiction
- we don’t have clear understanding of how they influence each other BUT they definitely do
