Psychostimulants increase locomotion through stimulation of VTA DA neurons (Vanderschuren and Kalivas, 2000). To investigate the response of SNX27DA KO mice to psychostimulants, we injected cocaine (20 mg/kg; i.p.) and immediately measured the total distance traveled over 30 minutes in an activity chamber. In WT and Dat-Cre+/− controls, cocaine increased locomotor activity by ~3-fold, 3.2 ± 0.5 fold for WT, n=6; 2.7 ± 0.4 fold for DAT-Cre+/−, n=16 (Figure 7C,D). By contrast, a single injection of cocaine increased locomotor activity by 8.0 ± 1.7 fold (n=14) in SNX27DA KO mice (Figure 7C,D), suggesting that the reduced GABABR-activated GIRK currents contributed to the heightened response to cocaine. To determine if the change in GABABR-activated GIRK signaling alone was sufficient to alter the response to cocaine, we took advantage of the finding that GABABR-activated GIRK currents and GABAB-dependent inhibition of firing were restored in SNX27DA KO mice injected with AAV DIO GIRK2a-eYFP (Figure 6B & Figure 8B). We next investigated the effect of cocaine in SNX27DA KO mice with AAV DIO GIRK2a-eYFP injected into VTA. Remarkably, the increase in locomotor activity produced
