GABAB receptors have been implicated in reducing addictive behaviors (Tyacke et al., 2010). GABAB receptors in DA neurons are selectively activated by GABAergic ventral pallidum projections to VTA (Sugita et al., 1992). Silencing ventral pallidum GABAergic afferents onto the VTA increases the population activity of DA neurons and extra-synaptic dopamine release in nucleus accumbens (Floresco et al., 2003) and could represent a mechanism by which diminished GABABR-GIRK currents by SNX27 trafficking of GIRK channels affect dopamine-dependent behaviors. Together with increased cortical expression of SNX27 following psychostimulant administration (Kajii et al., 2003) and the established role of GIRK channels in cocaine response (Morgan et al., 2003), these data identify a novel SNX27-dependent mechanism of inhibitory plasticity in DA neurons as a potential therapeutic intervention point for addiction and other psychiatric disorders of dopamine dysregulation.
