A comparison of the effects of 6-beta naltrexol and naltrexone on the consumption of ethanol or sucrose using a limited-access procedure in rats.
We recently reported that 6-beta naltrexol, the major metabolite of naltrexone in humans, reduced ethanol consumption in rats. Two new experiments were designed to compare 6-beta naltrexol and naltrexone across three dose levels on an ethanol or sucrose baseline using a limited-access procedure in Wistar rats. The results of Experiment 1 showed that both 6-beta naltrexol and naltrexone reduced ethanol consumption across a range of doses. An in vivo assay showed that naltrexone was approximately 25 times more potent than 6-beta naltrexol at comparable ED50 doses. In addition, there was no indication of systematic development of tolerance to the effect of either drug across the 4 days of drug administration. In Experiment 2, both 6-beta naltrexol and naltrexone reduced the consumption of a sucrose solution using a limited-access procedure. The implications of these data for the development of pharmacotherapeutic agents capable of reducing drinking in recovering alcoholics are discussed.
Stromberg
Michael F
MF
Department of Psychiatry, Center For Studies of Addiction, University of Pennsylvania, Philadelphia, PA 19104, USA. stromberg_m@mail.trc.upenn.edu
Rukstalis
Margaret R
MR
Mackler
Scott A
SA
Volpicelli
Joseph R
JR
O'Brien
Charles P
CP
D000428:Alcohol Drinking / Q000188:drug therapy*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000431:Ethanol; C010410:6 beta-hydroxynaltrexone; D013395:Sucrose; D009271:Naltrexone