Effect of Mu Opioid Receptor Blockade on Alcohol Intake in Rats Bred for High Alcohol Drinking

KRISHNAN-SARIN, S., G. S. WAND, X.-W. LI, T.-K. LI, P. S. PORTOGHESE AND J. C. FROEHLICH. Effect of mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking. PHARMACOL BIOCHEM BEHAV 59(3) 627–635, 1998.—Beta-funaltrexamine (beta-FNA), a selective mu opioid receptor antagonist, when administered in doses of 10.0, 15.0, and 20.0 mg/kg b.wt., decreased alcohol but not water intake in a dose-dependent manner in rats selectively bred for high alcohol intake (HAD line). Beta-FNA also suppressed the intake of a saccharin solution containing alcohol without altering the intake of a similar solution without alcohol. The results suggest that beta-FNA may prove useful as a pharmacotherapeutic agent for the treatment of alcohol dependence. In a second study, pituitary beta-endorphin gene expression (proopiomelanocortin or POMC messinger ribonucleic acid—mRNA) was compared in another pair of rat lines selectively bred for high or low alcohol intake (alcohol-preferring or P and alcohol-nonpreferring or NP lines). A repeated alcohol challenge (1.0 g/kg b.wt./day, IP for 4 days) produced a greater increase in POMC mRNA in the anterior and neurointermediate lobes of the pituitary of P rats compared with NP rats. The results suggest that a genetic predisposition toward high alcohol drinking may be associated with increased responsiveness of the opioid system to alcohol.