alcohol pt 2

opoids and alcohol (acute)

increases endogenous opioid (endophrin) production and release

increase gene expression of both endorphin and enkephalin in selected brain areas of rats

opoids and alcohol (chronic)

reduces gene expression, making less peptides available for release

in humans leads to reduced brain levels of endorphin

• may contribute to dysphoria that accompanies chronic alcohol use and withdrawal

opoids (endogenous)

release of DA in mesolimbic neurons is regulated by opioids in the VTA and in the NAC

• alcohol induced opioid release may produce reinforcement by modulating DA

opoid and alcohol reinforcement

opioid receptor antagonist reduce alcohol self admin

• naloxone and naltrexone significantly reduce alcohol self admin

• u opoid receptor KO mice fail to self adminster ethanol

endogenous opioid system

are more responsive to the effects of alcohol in rat strains bred for alcohol preference

• higher baseline levels of u-opioid receptors in NAC and amygdala

AUD

alcohol use disorder

• chronic relapsing brain disease characterized by compulsive alcohol use, loss of control over alcohol intake and a negative emotional state when not using

detoxification

alcohol use is stopped and withdrawal symptoms are treated until severe abstinence syndrome (e.g. acute phase) has ended

withdrawal symptoms are strong motivators and can be physiologically dangerous

detoxification drugs

involves substituting and benzodiazepine chlordiazepoxide or diazepam

prevents alcohol withdrawal including seizures and DTs

• dose is gradually reduced, withdrawal symptoms are reduced

pharmacotherapeutic treatment

strategies

• making drinking unpleasant

• reduce alcohol’s reinforcing qualities

• reduce withdrawal symptoms

• disulfiram, naltrexone, acamprosate

disulfiram

1949

• inhibits aldh, drinking even 1 oz of alcohol results in flushing, pounding heart, nausea, vomitting,

• compliance on the drug because it only works if the individual stays on the drug

• doesnt work on craving

naltrexone

upoid receptor antagonist

• reduces the high associated with alcohol—> alcohol loses its rewarding effects and becomes less reinforcing

• improves abstinence rates

• PO

• longer lasting for long term dependence

naloxone

rapid onset, short acting, not bioavaliable po

acamprostate

2004

• a partial antagonist of NDMA receptor

• blocks Glu release during withdrawal

• restores basal GABA level in dependent rats

• reduces some of the brain’s hyperexcitability associated with alcohol withdrawal

alcohol is a

carcinogen