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

Nicholas J. Grahame, Anne K. Mosemiller, Malcolm J. Low, Janice C. Froehlich

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Alcohol-induced activation of the opioid system may contribute to the reinforcing properties of alcohol. This study investigated whether elimination of β-endorphin (BE) synthesis via site-directed mutagenesis in embryonic stem cells would alter alcohol intake in mice. Both BE-deficient and wildtype (WT) mice generated from the targeted stem cells were backcrossed for nine generations onto a C57BL/6 background, and were maintained with ad libitum 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 days) or chronic (5 weeks) alcohol deprivation, and scheduled access following six doses of naltrexone (0.125-16.0 mg/kg BW, ip) or saline treatment. Alcohol intake was similar in BE-deficient and WT mice given chronic access to alcohol, but greater in BE-deficient compared with WT mice during the first 10 days of scheduled access to alcohol, but not after more extensive experience with scheduled access. BE-deficient, but not WT mice, increased alcohol intake following 2 days, but not 1 day or 5 weeks, of deprivation. Naltrexone reduced alcohol drinking both in BE-deficient and WT mice, suggesting that drinking is mediated, in part, by activation of opioid receptors in both genotypes.

Original languageEnglish (US)
Pages (from-to)759-766
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume67
Issue number4
DOIs
StatePublished - Dec 1 2000

Keywords

  • β-Endorphin-deficient mice
  • Alcohol deprivation effect
  • Alcohol preference

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

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