A comparison of the effects of 6-β naltrexol and naltrexone on the consumption of ethanol or sucrose using a limited-access procedure in rats

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2002-05, Vol.72 (1), p.483-490
• Main Authors: Stromberg, Michael F, Rukstalis, Margaret R, Mackler, Scott A, Volpicelli, Joseph R, O'Brien, Charles P
• Format: Article
• Language: English
• Subjects: 6-β Naltrexol; Alcohol Drinking - drug therapy; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Dose-Response Relationship, Drug; Ethanol; Ethanol - antagonists & inhibitors; Ethanol - pharmacology; Male; Medical sciences; Naltrexone; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Naltrexone - therapeutic use; Rats; Rats, Wistar; Sucrose; Sucrose - antagonists & inhibitors; Sucrose - pharmacology; Toxicology
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(02)00721-9

We recently reported that 6-β naltrexol, the major metabolite of naltrexone in humans, reduced ethanol consumption in rats. Two new experiments were designed to compare 6-β 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-β 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-β naltrexol at comparable ED 50 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-β 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.