Binge ethanol consumption-associated behavioral impairments in male mice using a gelatin-based drinking-in-the dark model

Abstract

Background: Acute intoxication caused by binge ethanol drinking is linked to widespread impairments in brain functions. Various alcohol administration paradigms have been used in animals to model the heterogeneous clinical manifestation of intoxication in people. It is challenging to model a procedure that produces "visible intoxication" in rodents; however, manipulation of variables such as route of alcohol administration, time of availability, frequency, and duration and amount of ethanol exposure has achieved some success. In the current study, we employed a modified drinking-in-the-dark model to assess the validity of this model in producing "post-ethanol consumption intoxication" impairments following prolonged repeated daily voluntary "binge" ethanol consumption.

Methods: Adult male C57BL/6J mice were allowed a daily 3-h access to non-alcoholic plain or ethanol-containing gel during the dark cycle for a total of 83 days. After the initial 2-month daily DID, ethanol intake patterns were intensely characterized during the next 3 weeks. Immediately following the last DID session (day 83), plain and ethanol gel-consuming mice were then subjected to behavioral tests of locomotor ability and/or anxiety (cylinder, wire grip, open field) followed by blood ethanol concentration measurement.

Result: Mice exhibited a relatively consistent ethanol consumption pattern during and across daily access periods. Ethanol intake of individual mice positively correlated with blood ethanol concentration that averaged 61.64 ± 2.84 mg/dL (n = 12). Compared to the plain gel-consuming control mice, ethanol gel mice exhibited significant locomotor impairment as well as anxiety-like behavior, with the magnitude of impairments of key indices well correlated with blood ethanol levels.

Conclusion: The gelatin vehicle-based voluntary ethanol drinking-in-the-dark model reliably produced post consumption acute movement impairments as well as anxiety-like behaviors even after 2 months of daily binge ethanol consumption in male mice. Taken together, this mouse binge ethanol model should facilitate the investigation of mechanisms of binge drinking in subjects chronically abusing ethanol and the search for effective novel treatment strategies.

Keywords: anxiety; binge drinking; ethanol; intoxication; locomotion.