COMPARISON OF COCAINE AND GBR-12935 - EFFECTS ON LOCOMOTOR-ACTIVITY AND STEREOTYPY IN 2 INBRED MOUSE STRAINS

The current study compares the acute and long-term effects of GBR 1293 5 and cocaine on locomotor activity and stereotypy in two genetically distinct strains of mice. Although cocaine stimulated locomotor activi ty maximally in both strains at 32 mg/kg, a single injection of cocain e stimulated locomotion to a greater degree in DBA/2J mice than in C57 BL/6J mice. In contrast, GBR 12935 elevated locomotion to a greater ex tent in C57BL/6J mice at the maximally active dose of 10 mg/kg. The st imulant effects of cocaine diminished to near control levels in DBA/ZJ mice upon repeated injections, whereas cocaine-induced locomotion rem ained relatively consistent in C57BL/6J mice. Locomotor stimulation by GBR 12935 remained consistent in both strains with repeated injection s. DBA/ZJ mice became sensitized to cocaine-induced stereotypy with re peated injections. Cocaine induced no stereotypy in C57BL/6J mice on a ny test day. No stereotypies were induced by GBR 12935 in either strai n on any test day. Moreover, no cross-sensitization between cocaine an d GBR 12935 was observed. These results demonstrate differences in the behavioral effects of two dopamine uptake inhibitors, and suggest tha t genetically controlled factors other than dopamine uptake inhibition contribute to the acute and adaptive behavioral responses to cocaine.