Naltrexone and alcohol drinking in mice lacking beta-endorphin by site-directed mutagenesis

Alcohol-induced activation of the opioid system may contribute to the reinf orcing properties of alcohol. This study investigated whether elimination o f beta -endorphin (BE) synthesis via site-directed mutagenesis in embryonic stem cells would alter alcohol intake in mice. Both BE-deficient and wildt ype (WT) mice generated from the targeted stem cells were backcrossed for n ine generations onto a C57BL/6 background, and were maintained with ad libi tum food and water. Mice had access to alcohol(10% v/v) under the following conditions: 24 h, scheduled access for 2 h/day, following acute (1 or 2 da ys) or chronic (5 weeks) alcohol deprivation, and scheduled access followin g six doses of naltrexone (0.125-16.0 mg/kg BW, ip) or saline treatment. Al cohol intake was similar in BE-deficient and WT mice given chronic access t o alcohol, but greater in BE-deficient compared with WT mice during the fir st 10 days of scheduled access to alcohol, but not after more extensive exp erience with scheduled access. BE-deficient, but not WT mice, increased alc ohol intake following 2 days, but not 1 day or 5 weeks, of deprivation. Nal trexone reduced alcohol drinking both in BE-deficient and WT mice, suggesti ng that drinking is mediated, in part, by activation of opioid receptors in both genotypes. (C) 2001 Elsevier Science Inc. All rights reserved.