The alcohol-preferring C57BL/6 mice present an enhanced sensitivity of the hypothalamic beta-endorphin system to ethanol than the alcohol-avoiding DBA/2 mice.

One of the systems proposed to mediate the reinforcing effects of ethanol is the endogenous opioid system. The objective of the present studies was to investigate the effects of various concentrations of ethanol on the release of beta-endorphin (beta-EP) by the hypothalami of mice showing either high (C57BL/6) or low (DBA/2) voluntary ethanol consumption. Results indicated that the release of beta-EP, either under basal conditions or in the presence of ethanol, was higher from the hypothalami of the C57BL/6 than of the DBA/2 mice. After exposure to various concentrations of ethanol, it was observed that for both strains of mice, low concentrations of ethanol (10, 20 and 25 mM) induced a more pronounced increase in the release of hypothalamic beta-EP than high concentrations of ethanol (30 and 60 mM) leading to an inverse U-shaped dose-response curve. Maximum release for both strains of mice was obtained at 20 mM ethanol. High-performance liquid chromatography analysis indicated that beta-EP 1-31 in the nonacetyl, opiate active form was the major form of the beta-EP-sized peptides released by the hypothalami of both strains of mice. The tissue content of beta-EP-like peptides was similar in the hypothalami of both strains of mice; however, the content of pro-opiomelanocortin mRNA was significantly higher in the hypothalami of the C57BL/6 mice. These genetically determined differences in the basal activity and in the response of the hypothalamic beta-EP system to ethanol may be partially responsible for the different ethanol consumption exhibited by these two strains of mice.