Genetics of ethanol-induced locomotor activation: detection of QTLs in a C57BL/6JxDBA/2JF(2) intercross

Moderate doses of ethanol (1-2 g/kg) markedly increase locomotor activity i n some inbred mouse strains, for example, the DBA/2J (D2), but have relativ ely little effect in other strains, for example, the C57BL/6J (B6). In the present study, we conducted a genome-wide search in a B6D2 F-2 intercross ( N = 925) for quantitative trait loci (QTLs) associated with the locomotor r esponse. A QTL with a LOD score of 8.4 was detected on Chromosome (Chr) 2; this QTL accounted for 11.4% of the phenotypic variance and approximately 3 0% of the genetic variance. The QTL on Chr 2 is in the same general region as QTLs previously described for ethanol preference/consumption (Rodriguez et al. Alcohol Clin Exp Res 19, 367, 1995; Melo et al. Nat Genet 13, 147, 1 996; Phillips et al. Mamm Genome, in press), acute ethanol withdrawal (Buck et al. J. Neurosci 17, 3946, 1997) and nitrous oxide withdrawal severity ( Belknap et al. Behav Genet 23, 213, 1993). A logical candidate gene in the region of interest is the enzyme which synthesizes GABA, glutamic acid deca rboxylase 1 (GadI).