Effect of mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking.
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 messenger 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.
Krishnan-Sarin
S
S
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5124, USA.
Wand
G S
GS
Li
X W
XW
Portoghese
P S
PS
Froehlich
J C
JC
D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D001345:Autoradiography; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*
D009292:Narcotic Antagonists; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D011333:Pro-Opiomelanocortin; C024524:beta-funaltrexamine