Effect of pattern and number of chronic ethanol exposures on subsequent voluntary ethanol intake in C57BL/6J mice

Rationale: We previously demonstrated that chronic ethanol exposure and withdrawal experience significantly increased subsequent voluntary ethanol intake in C57BL/6J mice. This study was conducted to examine chronic ethanol conditions that optimize this enhanced ethanol-drinking behavior. Objectives: The purpose of this study was to examine whether the pattern and/or number of chronic ethanol exposures influence subsequent ethanol intake. Methods: C57BL/6J mice were trained to drink ethanol (15% v/v) in a limited access situation (2 h/day) until stable intake was achieved. In experiment 1, mice received two cycles of chronic ethanol exposure delivered either in an intermittent [multiple withdrawal (MW)] or continuous [continuous exposure (CE)] pattern. One week of daily drinking sessions followed each exposure. In experiment 2, mice received either two or four cycles of chronic intermittent ethanol exposure (MW), each followed by a week of testing sessions. Three additional weeks of ethanol intake testing followed the last ethanol (or air) exposure. Results: Experiment 1: Only the MW group evidenced a significant increase in ethanol intake compared to controls after the first chronic ethanol exposure. Both MW and CE groups consumed more ethanol than controls after the second ethanol-exposure period. Experiment 2: Ethanol intake in MW mice compared to controls significantly increased after two or four cycles of chronic ethanol exposure/withdrawal, and this heightened ethanol intake lasted longer in mice that received four cycles of chronic intermittent ethanol exposure. Conclusions: Increased voluntary ethanol intake after chronic ethanol exposure and withdrawal experience may be accelerated by intermittent (as opposed to continuous) ethanol exposure, and the effect may last longer with increased number of such experiences.