Effects of Acute and Repeated Ethanol Exposures on the Locomotor Activity of BXD Recombinant Inbred Mice

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Abstract
Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, ip) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38–0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD Rl strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulant/sensitizing effects of EtOH and EtOH consumption.