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 in response to cocaine returned to control levels in SNX27DA KO mice expressing GIRK2a (Figure 8B,C). Reduction of the amplitude of fast GABA-evoked IPSCs can increase excitability DA neurons and enhance the locomotor response to morphine (Parker et al., 2011), but we did not observe a change in frequency or amplitude of sIPSCs in SNX27DA KO neurons. Thus, alterations in the amplitude of GABABR-activated GIRK currents in VTA DA neurons appears tightly correlated with the response to cocaine, implicating SNX27 as a potential therapeutic target for dopamine-dependent behavioral disorders such as addiction.
