Confirmation of quantitative trait loci for cocaine-induced activation in the AcB/BcA series of recombinant congenic strains.

Individual differences in the psychomotor stimulant effects of cocaine are influenced by genetic factors. Several quantitative trait loci (QTL) have been identified for cocaine-induced locomotor activation using the AXB/BXA recombinant inbred series of strains derived from the A/J (A) and C57BL/6J (B6). The aim of the present study was to conduct an independent analysis of cocaine-induced activation in the AcB/BcA recombinant congenic strains. The AcB/BcA RC series consists of 37 inbred strains derived from reciprocal backcrosses between the A and B6, followed by systematic inbreeding. Locomotor activity was measured in a computerized open-field apparatus following intraperitoneal administration of saline and cocaine (20 mg/kg). Linkage maps constructed with 625 informative microsatellite markers were used to identify chromosomal regions associated with cocaine difference scores. Significant (P < 0.00001) regions were identified on chromosomes 1 (13-25.7 and 36.9-58.5 cM), 5 (1-28 and 84-86 cM), 6 (7-26.35 cM), 7 (9.4-27.8 cM), 9 (9-28 cM), 13 (21-37 cM), 16 (36-66 cM), 17 (22.5-24.5 cM) and 18 (45-48 cM). Multiple regression analysis demonstrated that a subset of four markers, including D5Mit182 (24 cM), D5Mit409 (84 cM), D7Mit83 (26.5 cM) and D13Mit54 (35 cM), accounted for 90% of the genetic variance in cocaine difference scores. The results of the present study provide confirmation for a number of QTL on chromosomes 1, 5, 6, 9, 16 and 17 which were previously identified in the recombinant inbred AXB/BXA and BXD strains that share a common B6 ancestor.