CHROMOSOMAL MAPPING OF LOCI INFLUENCING SENSITIVITY TO COCAINE-INDUCED SEIZURES IN BXD RECOMBINANT INBRED STRAINS OF MICE

Among inbred mice, genetic factors mediate differences in sensitivity to the convulsant properties of cocaine; however, the gene(s) underlyi ng cocaine's effects have not been identified. To help elucidate the g ene(s) responsible for cocaine seizure susceptibility, we used recombi nant inbred-quantitative trait loci (RI-QTL) analyses to identify chro mosomal loci associated with cocaine-induced seizures. RI-QTL analyses seek to identify associations between a quantitative measure of a par ticular phenotype and one or more previously mapped marker genes acros s a panel of RI strains. This report describes an RI-QTL analysis of c ocaine seizure susceptibility among 26 BXD RI strains. These strains s howed a skewed, bimodal range of seizure susceptibility which could be the result of one or more modifying genes acting in concert with a ma jor gene to influence cocaine sensitivity. Correlating the percent sei zures displayed by each strain following 60 mg/kg cocaine with chromos omal marker data for these strains revealed a number of significant co rrelations clustered in two regions on chromosomes 12 and 6. This is t he first identification of putative chromosomal loci associated with a cocaine-related phenotype and should facilitate identification of the gene(s) underlying cocaine toxicity and other cocaine-related phenoty pes.