CHARACTERIZATION OF DOPAMINE TRANSPORTER AND LOCOMOTOR EFFECTS OF COCAINE, GBR-12909, EPIDEPRIDE, AND SCH-23390 IN C57BL AND DBA MICE

C57BL/6 and DBA/2 mice were used to examine genetic differences in loc omotor activating effects of acute cocaine administration and to deter mine whether differences were mediated by dopaminergic systems. C57BL/ 6 mice were less activated than DBA/2 mice at 5 and 10 min after 10 an d 15 mg/kg cocaine. HPLC analysis showed equivalent brain cocaine conc entrations in the two strains at 5 and 10 min after 10, 15, or 20 mg/k g doses. The selective dopamine uptake inhibitor, GBR 12909, at 5 and 7.5 mg/kg, produced greater locomotor activation in DBA/2 mice than in C57BL/6 mice. However, binding studies with the selective dopamine up take ligand [H-3]GBR 12935, revealed no between-strain difference in K -d or B-max in caudate putamen (CP) or nucleus accumbens (NA) membrane s. Competition assays using unlabeled dopamine to compete for [3H]GBR 12935 binding in CP or NA membranes showed no between-strain differenc e by brain region. The specific D-1 or D-2 antagonists, SCH 23390 or e pidepride, respectively, produced dose-dependent decreases in locomoto r activity but there were no between-strain differences. However, epid epride, at a dose of 0.003 mg/kg, completely reversed cocaine-induced (15 mg/kg) activation in both strains. These findings show that C57BL/ 6 and DBA/2 mice differ in dopamine-related behaviors and suggest that dopaminergic processes may mediate genetic differences in cocaine sen sitivity.