Alcohol Flashcards
safe drinking levels
women -> 10 drinks/week; no more than 2/day
men -> 15 drinks/week; no more than 3/day
alcohol addiction vs alcoholism
alcohol addiction = medical disorder
alcoholism = not recognized as diagnosis
terms used to describe unhealthy levels of alcohol use
4 elements
- problematic alcohol use
- alcohol use disorder
- alcohol abuse
- as well as scores on structured interviews such as AUDIT
trajectory of alcohol effects
6 elements
stage #1 -> stimulation
1. relaxation (after 1-2 drinks)
2. disinhibition (after 3-4 drinks)
stage #2 -> sedation
3. impaired motor function
4. stupor
5. coma
6. death (in a single bout)
ethanol metabolism
4 elements
- ethanol -> acetaldehyde (via alcohol dehydrogenase/ADH)
- acetaldehyde -> acetate (via aldehyde dehydrogenase/ALDH)
- acetate enters tricyclic acid cycle -> converted to CO2
- reactions dependent on NAD and mt electron transport
when is ROS produced during ethanol metabolism
when ethanol is metabolized in peroxisomes
where are ADH and ALDH expressed
mostly in liver, some in parts of digestive tract
effect of regular alcohol consumption on ADH and ALDH
upregulation of enzymes
what causes symptoms of hangover
2 elements
- excess of aldehyde
- ROS
what happens when deficiency of ALDH
build up of aldehyde -> protection against addiction
effects of initial use of alcohol (2) + neurobiology involved (2)
- positive reinforcement + reward phase
- increased DA + opioid reward systems involved
effects of heavy or binge drinking (2) + neurobiology involved (4)
- tolerance (can drink large quantities/DAr become intolerant) + regulated drug-seeking
- neuroadaptations in DA, glutamate, GABA and endocannabinoid systems
effects of withdrawal (4) + neurobiology involved (2)
- negative affect + associated with anxiety + depression + anhedonia
- neuroadaptations in reward and stress systems drive compulsive consumption + increased value of drug stimuli and reduced sensitivity to natural reinforcers
effect of craving
compulsive drug seeking
mechanism of DA release in alcohol reward phase
disinhibiting GABA control of VTA DA release, via opioid peptide
acute effects in brain during reward phase
3 elements
- 5HT and NE released
- release pharmacological levels of DA activating D1 receptors
- initiate a ‘liking’ for the drug
primary site of reward phase activity
mesolimbic -> VTA and dorsal striatum
changes in brain during tolerance, regulated relapse phase
4 elements
- alcohol-dependent epigenetic changes become stabilized
- changes in NMDAr and AMPAr -> reinforces excessive drug taking
- glutamate projections to PFC still effective, but aversive signals competing with positive reinforcement
- midbrain stress system (CeAmyg, BNST, NAcc) increasingly active
brain effects in withdrawal phase
3 elements
- activation of CeAmyg stress circuit
- decreased levels/efficacy of DA, 5HT, enkephalin, endocannabinoids
- increased levels of CRH, CRH receptors, dynorphin, orexin, substance P
brain changes in compulsive drug seeking phase
4 elements
- morphological changes in striatal neurons
- changes in signalling
- CRH and glutamatergic systems hypersensitive in withdrawn individuals
- GABA dysregulated
relation bw D1 and GABAr
activation of D1 facilitates GABA-Ar sensitivity
neurons important in withdrawal phase
VTA GABA neurons
activation of CeAmyg stress circuit in withdrawal phase leads to
increasingly negative affective states
anatomy involved in compulsive drug seeking phase
3 elements
PFC, HC, corticostriatal glutamate system
projections important in DA release in compulsive drug-seeking phase
glutamatergic projections to PFC
what mediates craving
strong glutamate signals
what circuits does stress-induced relapse involve
CRH and NE elements in CeAmyg
neurotransmitter targets of ethanol
6 elements
- GABA
- glutamate
- DA
- CRH
- opioid
- Ach
cardinal features of alcohol use disorders
3 elements
- pathological use of alcohol
- social, occupational or legal impairment; medical consequences
- tolerance and withdrawal
objective criteria for alcohol use disorders
4 elements
- medical complications (cirrhosis, cardiomyopathy, peripheral neuropathy, cerebellar degeneration, dementia)
- impaired social relationships (disintegration of family, loss of friends)
- inability to fulfill role obligations (work, school)
- substance related legal problems
behavioral criteria for alcohol use disorders
6 elements
- daytime intoxication, morning drinking
- persistent desire or unsuccessful efforts to reduce substance use
- increased time spent in obtaining drug or in thinking about obtaining drug
- other social and recreational activities abandoned or reduced in favor of substance abuse
- increased use of drug despite physical impairments
- complications of intoxication (blackouts)
diseases secondary to alcoholism
3 elements
- liver: hepatitis, fatty liver, cirrhosis
- cancers: upper GI, liver, breast, lower GI (involves toxic byproduct of metabolism)
- brain disease: dementia, hallucinosis, FAS (vulnerability to psychosis)
neurobehavioral problems in FAS
7 elements
- attention
- memory
- motor control
- language
- impulse control
- cognitive function
- coping skills
dangers of adolescent drinking
3 elements
- death and major injuries (overdose, falls, burns, drowning, suicide, etc.)
- impaired jugdement and risky behavior (aggressiveness, violence, promiscuity, polydrug abuse)
- legal involvement
myths of adolescent drinking
2 elements
- the earlier one starts drinking, the more likely they will become addicted
- will lead to irreparable brain damage
anatomical problems in FAS
3 elements
- facial dysmorphology + holoprosencephaly
- microencephaly
- growth retardation + mental retardation
comorbidities of drinking
4 elements
- smoking
- anxiety disorders
- depression
- personality traits (impulsivity)
treatments for AUD
4 elements
- AA & 12-step programs
- CBT (not effective if no motivation to stop/reduce)
- brief interventions (motivational interviewing)
- supportive medication
pharmacological interventions to drink less
3 elements
- disulfuram: blocks ALDH, very aversive
- naltrexone: blocks opioid release -> blocks GABA disinhibition on NAcc DA release (useful in early stages)
- acamprosate: GABA-Ar antagonist (useful in later stages)
pharmacological interventions to drink less that aren’t approved
3 elements
- anxiolytics
- compounds that target CRH cascade
- GLP1 antagonists; FGF1 antagonists; ozempic (effective to decrease drinking, not for addiction)
environmental aspects involved in AUD
9 elements
- ethanol itself
- education
- socioeconomic status
- religious prohibitions
- occupation
- childhood or sexual abuse
- cognitive function
- stress and coping mechanisms
- temperament and personality
alcoholism in asians
3 elements
- chinese -> moderate, infrequent drinking (just important social occasions)
- japanese -> increase in consumption
- koreans -> extremes (abstinence or excess)
genes responsible for alcoholism
2 elements
- ADH -> ADH-2 & ADH-3 associated with alcoholism; ADH-3 predisposition to FAS
- ALDH -> ALDH-2 mutation confers reduced rate of acetaldehyde clearance (reduced risk of alcoholism)
strongest linkage signals for an addiction risk factor
3 elements
- FTO (diabetes, fat distribution)
- DRD2 (regulation of DAr)
- PDE4B (NT pathways)
predispositions to becoming addicted to alcohol
3 elements
- epigenetics
- reduced resting EEG amplitude
- blunted subjective response to ethanol challenge (FH+)
relation between acute ethanol administration and csf metabolites
acute ethanol administration increases csf metabolites of DA and 5HT
levels of release of DA and drinking
animals that have lower release of DA drink more (reduced response (low LR) predicts high preference)
results of study of adolescent monkeys with social exposure to alcohol
4 elements
- alc preference increased after 6 or 12 months of social alc exposure
- after 12 months of social ethanol exposure -> modest effect of social role models with high alc preference
- 12 or 24 months after cessation of social ethanol access -> main predictor of consumption level was baseline ethanol preference
- adolescent exposure to ethanol -> transient effect in individuals with low/moderate genetic vulnerability for preference drinking, but persistent effect in individuals with high genetic vulnerability
implications of study of adolescent monkeys with social exposure to alcohol
2 elements
- early heavy use of beverage ethanol = marker of vulnerability (not environmental gateway to AUDs)
- gene-environment interactions in high-risk individuals mandate individualization of early screening and treatment programs
services to families
3 elements
- counselling for susceptibility to alcoholism
- empiric risks and education
- counselling regarding prenatal drug use
low and high LR responsiveness (amygdala-PFC connectivity) to angry and happy faces when drinking alcohol (compared to placebo)
low LR: decreased response to angry faces compared to placebo; increased response to happy faces compared to placebo
high LR: no difference in response to angry faces compared to placebo; increased response to happy faces compared to placebo
raclopride function
estimate DA release and binding
raclopride binding and ethanol
decreased raclopride binding in subjects with high LR (low DA release if high LR, higher DA release if low LR)
