The reduction of GABABR-activated GIRK currents in VTA DA neurons of SNX27DA KO mice afforded us with a unique opportunity to explore the behavioral effects of the subtle change in electrical properties of VTA DA neurons. In previous experiments with GABAB-R agonists or antagonists, it was not possible to selectively target GABABR-activated GIRK s in DA neurons (Frankowska et al., 2009; Kalivas and Stewart, 1991). Previous studies have shown that firing of VTA DA neurons is critically involved in reward processing and the response to drugs of abuse (Kalivas and Stewart, 1991; Parker et al., 2011; Schultz, 2007; Tsai et al., 2009). We therefore investigated whether the reduced GABABR-activated GIRK currents in VTA DA neurons of SNX27DA KO mice would affect the response to cocaine. Interestingly, basal locomotor activity of SNX27DA KO mice was ~40% higher upon initial exposure to a novel open field environment, as compared to wild-type or DAT-Cre+/− control mice (Figure 7A). However, SNX27DA KO mice occupied the center of the chamber for the same amount of time as controls (Figure 7B), ruling out altered thigmotaxis (wall-hugging) or anxiety levels as possible explanations for enhanced activity levels.
