Repeated cycles of binge-like ethanol (EtOH)-drinking in male C57BL/6J mice augments subsequent voluntary EtOH intake but not other dependence-like phenotypes

Abstract

Background: Recently, procedures have been developed to model specific facets of human alcohol abuse disorders, including those that model excessive binge-like drinking (i.e., "drinking-in-the-dark," or DID procedures) and excessive dependence-like drinking (i.e., intermittent ethanol [EtOH] vapor exposure). Similar neuropeptide systems modulate excessive EtOH drinking stemming from both procedures, raising the possibility that both paradigms are actually modeling the same phenotypes and triggering the same central neuroplasticity. Therefore, the goal of this present project was to study the effects of a history of binge-like EtOH drinking, using DID procedures, on phenotypes that have previously been described with procedures to model dependence-like drinking.

Methods: Male C57BL/6J mice first experienced 0 to 10 four-day binge-like drinking episodes (3 days of rest between episodes). Beginning 24 hours after the final binge-like drinking session, mice were tested for anxiety-like behaviors (with elevated plus maze [EPM] and open-field locomotor activity tests), ataxia with the rotarod test, and sensitivity to handling-induced convulsions (HICs). One week later, mice began a 40-day 2-bottle (water vs. EtOH) voluntary consumption test with concentration ranging from 10 to 20% (v/v) EtOH.

Results: A prior history of binge-like EtOH drinking significantly increased subsequent voluntary EtOH consumption and preference, effects most robust in groups that initially experienced 6 or 10 binge-like drinking episodes and completely absent in mice that experienced 1 binge-like drinking episode. Conversely, a history of binge-like EtOH drinking did not influence anxiety-like behaviors, ataxia, or HICs.

Conclusions: Excessive EtOH drinking stemming from DID procedures does not initially induce phenotypes consistent with a dependence-like state. However, the subsequent increases in voluntary EtOH consumption and preference that become more robust following repeated episodes of binge-like EtOH drinking may reflect the early stages of EtOH dependence, suggesting that DID procedures may be ideal for studying the transition to EtOH dependence.

Keywords: Anxiety-Like; Ataxia; Binge-Like; C57BL/6J; Dependence; Ethanol; Seizure.

Fig. 1

A history of repeated cycles of binge-like ethanol (20%, v/v) drinking significantly augments subsequent 2-bottle choice voluntary ethanol consumption. Data points at each concentration of ethanol (v/v) represent an 8-day average, and data are expressed as mean g of ethanol consumed per kg of body weight per day (g/kg/day; A and C) or mean ethanol preference (ethanol consumed / total fluid intake; B and D). The top row represents data collected from Experiment 1 (A and B) and the bottom row represents data collected from Experiment 2 (C and D). Data are expressed as mean ± SEM. Significance legend (based on Bonferroni corrected t-tests): a = H₂0 < 6-cycles; b = 1-cycle < 6-cycles; c = H₂0 < 3-, 6-, and 10-cycles; d = H₂0 < 6- and 10-cycles; e = 1-cycle < 10-cycles. Significant differences between groups on the cycles main effect (indicated in B and D) are based on Bonferroni corrected t-tests.