We first measured basal activity levels and the motor-stimulatory effect of systemic cocaine (0-60 mg/kg) in wild-type and Girk−/− mice in a standard open-field environment (Fig. 1). Girk1−/− and Girk2−/− mice were similarly hyperactive during their initial and subsequent exposures to the novel environment (Fig. 1A). Cocaine triggered dose-dependent increases in motor activity in all groups (Fig. 1B). While none of the genotypes responded significantly to 3 mg/kg cocaine, Girk1−/− and Girk2−/− mice showed comparable and enhanced responses to 15 mg/kg cocaine. Maximal responses did not differ across genotypes, though they were observed at 15 mg/kg for Girk2−/− mice and at 30 mg/kg for the other three groups. Responses of Girk2−/− mice to 30 mg/kg were notably, though not significantly, smaller than those seen at the 15 mg/kg. Similarly, 60 mg/kg cocaine evoked sub-maximal responses in wild-type, Girk1−/−, and Girk3−/− mice.
