Alcohol-induced locomotor activation in C57BL/6J, A/J, and AXB/BXA recombinant inbred mice: strain distribution patterns and quantitative trait loci analysis

Rationale: Quantitative trait loci (QTLs) for initial sensitivity to alcoho l have been identified in a number of mouse strains (e.g. BXD); however, co nfirmation is required. Objectives: The present paper aimed to characterize the C57BL/6J, A/J, and PXB/BXA recombinant inbred (RI) strains of mice for basal and ethanol-induced locomotor activation as measured in an open fiel d and to provide provisional location of QTLs for these phenotypes. Methods : A/J and C57BL/6J mice were habituated to handling and then randomly assig ned to receive one of four alcohol doses (0, 0.5, 1.0, 2.0 g/kg). Subsequen tly, all available strains of the AXB/BXA RI were tested with the 2 g/kg do se of ethanol or vehicle control. Results: Simple regression and interval m apping were used initially to identify significant gene markers associated with ethanol-induced activation (calculated as total activity on alcohol da y-total activity on saline day. Subsequently, composite interval mapping (C IM) was used to increase the accuracy in mapping individual loci. Genetic m arkers on chromosomes 2, 3, 8, 13, 16, 18 and 19 were associated with ethan ol-induced activation. Conclusions: Three significant markers identified th rough CIM accounted for 86% of the genetic variance in the ethanol-induced activation. QTLs on chromosome 16 (45.6 cM) and 19 (24 cM) previously assoc iated with alcohol consumption in the AXB/BXA RI mice were found to overlap with QTLs for ethanol-induced activation identified in the present study.