Here, we sought insight into the DA-related phenotypes reported in Girk2−/− mice. We reasoned that if these phenotypes reflect the loss of Girk signaling in VTA DA neurons, they would be observed in Girk2−/− but not Girk1−/− mice. We applied a combination of behavioral, electrophysiological, and cell biological approaches to examine the impact of Girk1 and Girk2 ablation on neurotransmission within the mesolimbic reward pathway. Our findings indicate that loss of Girk signaling in midbrain DA neurons is not the primary cause of the DA-related phenotypes reported in Girk2−/− mice, and suggest instead that secondary adaptations that facilitate glutamatergic neurotransmission may play a role.
