Tolerance to Ethanol’s Ataxic Effects and Alterations in Ethanol-induced Locomotion Following Repeated Binge-like Ethanol Intake Using the DID Model

Abstract

Background: Tolerance to the behavioral and subjective effects of alcohol (ethanol) is thought to be a major predictive factor for the development of alcoholism. Evidence from rodent models has supported this view with those animals most likely to develop tolerance generally drinking and preferring ethanol more so than those resistant to it. Despite this evidence, very little is known about the behavioral relationships between ethanol-induced tolerance and consumption. The goal of this study was to evaluate the development of tolerance to the ataxic effects of ethanol using a mouse model of binge-like intake dubbed "Drinking in the Dark" (DID; Physiol Behav 2005, 84:53-63). We hypothesized that mice would become tolerant to the ataxic effects of ethanol as this behavior is known to be altered at the blood ethanol concentrations reached using this model (≥80 mg/dl). Methods: To evaluate this, we gave daily DID ethanol or water access sessions to male C57BL/6J (B6) mice and monitored ataxia (and in some cases locomotion) at various time points. Results: In general, mice given 14 consecutive days of ethanol access displayed tolerance to the ataxic effects of ethanol compared to water-drinking controls. These effects were coupled with alterations in locomotor behavior and in some cases differences in ethanol pharmacokinetics. Conclusions: Thus, we can conclude that tolerance to the behavioral effects of binge-like ethanol intake might play a key role in the daily maintenance of this behavior and that these effects may be evidence of important neuroadaptations involved in the development of alcoholism.