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.
Bibliographical noteFunding Information:
This research was supported, in part, by grants AA08312, AA08553, AA07611, and DA01533 from the PHS. We thank Dr. James Norton for statistical consultation and Dr. Ting-Kai Li for supplying us with selectively bred rats from the P, NP, and HAD lines.
- Alcohol drinking
- Alcohol preference
- Genetic selection
- Opioid antagonists
- Opioid receptors
- Pituitary gland