Central vs. peripheral mediation of opioid effects on alcohol consumption in free-feeding rats.
Although there is considerable evidence that pretreatment with low doses of opioid agonists can enhance, and opioid antagonists can reduce alcohol consumption in rats, little is known about the locus or mechanism of these effects. As a first approximation as to where the effect may occur, we compared the effects of an opioid agonist morphine (1, 3 and 10 mg/kg) and antagonist naltrexone (1, 3 and 10 mg/kg) that are known to act within the brain as well as the periphery, to those of an agonist-like drug loperamide (0.3, 1 and 3 mg/kg) and an antagonist methylnaltrexone (3, 10 and 30 mg/kg) that are known to act peripherally only. Free-feeding rats were initially trained to drink alcohol using a limited access paradigm, and when animals were drinking asymptotic amounts of 12% (w/v) alcohol, increasing doses of one of the four drugs or saline were administered IP to separate groups of rats 30 min prior to the hour-long daily drinking session. The results confirmed that the effects of the opioids on alcohol consumption are indeed mediated within the central nervous system in that morphine enhanced alcohol consumption but loperamide did not, naltrexone reduced alcohol consumption but methylnaltrexone did not, and naltrexone was able to block the morphine effect but methylnaltrexone failed to do so. An unexpected finding was that methylnaltrexone alone also increased alcohol consumption. Possible means by which this could occur, also supporting the idea of a central locus for the effect, as well as possible mechanisms by which opioids could influence alcohol consumption generally, are discussed.
Linseman
M A
MA
Addiction Research Foundation, Toronto, Canada.
D000428:Alcohol Drinking / Q000187:drug effects*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D004347:Drug Interactions; D008139:Loperamide / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011136:Polysorbates / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D009292:Narcotic Antagonists; D010880:Piperidines; D011136:Polysorbates; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone; D008139:Loperamide; D009020:Morphine