PT - JOURNAL ARTICLE AU - Heather S. Hain AU - John C. Crabbe AU - Susan E. Bergeson AU - John K. Belknap TI - Cocaine-Induced Seizure Thresholds: Quantitative Trait Loci Detection and Mapping in Two Populations Derived from the C57BL/6 and DBA/2 Mouse Strains DP - 2000 Apr 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 180--187 VI - 293 IP - 1 4099 - http://jpet.aspetjournals.org/content/293/1/180.short 4100 - http://jpet.aspetjournals.org/content/293/1/180.full SO - J Pharmacol Exp Ther2000 Apr 01; 293 AB - Seizures are a well known consequence of human cocaine abuse, and in rodent models, sensitivity to cocaine seizures has been shown to be strongly influenced by genotype. For example, several studies have reported significant differences between the C57BL/6 (B6) and DBA/2 (D2) inbred mouse strains in their sensitivity to cocaine-induced seizures. This prompted our use of the BXD recombinant inbred (RI) strain set and an F2 population derived from the B6 and D2 progenitor strains for further genetic analyses and for gene mapping efforts in this study. Cocaine was infused into the lateral tail vein, and the doses needed to induce a running bouncing clonic seizure and a tonic hindlimb extensor seizure were recorded for each mouse. In the BXD RI set, a genome-wide search was carried out for QTLs (quantitative trait loci), which are sites on a chromosome containing genes that influence seizure susceptibility. An F2population (B6D2F2, n = 408) was subsequently used as a second, confirmation step. Based on both RI and F2results, three QTLs emerged as significant (P < .00005): one for clonic seizures on chromosome 9 (distal), and two for tonic seizures on chromosomes 14 (proximal to mid) and 15 (distal). Two additional QTLs emerged as suggestive (P < .0015), both associated with clonic seizures on chromosomes 9 (proximal) and 15 (distal). Both QTLs on chromosome 9 were sex-specific, with much larger effects on the phenotype seen in females than in males. U.S. Government