hM4D-mediated inhibition of vHPC GAD65 neurons enhanced spontaneous and amphetamine-induced locomotor activity. GAD65-Cre mice expressing hM4D in GAD65 neurons of the vHPC were administered vehicle or CNO intraperitoneally. A, CNO significantly increased total distance traveled at 0.5 mg/kg (n = 4), 1 mg/kg (n = 10), and 2 mg/kg (n = 9) compared with vehicle treatment. *p < 0.05; **p < 0.01; ***p < 0.001. B–D, Distance traveled across 10 min bins was enhanced after 0.5 mg/kg CNO (p = 0.05; B); 1 mg/kg CNO (p = 0.007; C); or 2 mg/kg CNO (p < 0.001; D). E, Distance traveled after 1 mg/kg CNO was reduced by 0.02 mg/kg haloperidol pretreatment (n = 6) compared with vehicle pretreatment (n = 6). *p < 0.05. There were no significant differences between vehicle + vehicle–treated (n = 6) and haloperidol + vehicle–treated mice (n = 6). F, Distance traveled after vehicle and CNO was reduced by SCH23390 (n = 6). *p < 0.05. G, Amphetamine (1 mg/kg)-induced locomotor activity was significantly enhanced in CNO-treated (0.5 mg/kg, n = 8) compared with vehicle-treated mice (n = 8). p < 0.0001.