3 years ago

An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice

Despite acceptance that risk for alcohol use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many seen in multiple species, and can be experienced over a wide-ranging time course. In the present 3 studies, we developed a battery of withdrawal tests examining behavioral symptoms from multiple domains that could be measured over time in mice. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing 8 inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hrs. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using some apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), straub tail, backward walking and reductions in activity, but not changes in thermal pain sensitivity, hyperreactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should be reflecting the influences of different constellations of genes.

Publisher URL: www.sciencedirect.com/science

DOI: S0741832917308479

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