EFFECTS OF ACUTE AND REPEATED ETHANOL EXPOSURES ON THE LOCOMOTOR-ACTIVITY OF BXD RECOMBINANT INBRED MICE

Investigations of ethanol's (EtOH's) complex response profile, includi ng locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor acti vity responses to acute and repeated EtOH (2 g/kg, ip) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) a nd 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 loc omotor response to EtOH, acid 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimu lation. 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 phenot ypes. Acute locomotor response and locomotor sensitization were negati vely correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitizatio n induced by EtOH, suggest independence of genetic determination of lo comotor responses to acute and repeated EtOH exposure, and partially s upport a relationship between reduced sensitivity to the locomotor sti mulant/sensitizing effects of EtOH and EtOH consumption.