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Significance Activation of G protein-gated inwardly rectifying potassium (GIRK) channels inhibits neuronal activity in the brain, but details are lacking on how this important pathway influences neural circuits in the reward pathway. Here, we provide an example of where control of trafficking of GIRK channels by a cytoplasmic protein, sorting nexin 27, determines the sensitivity of mice to cocaine in a model of addiction known as locomotor sensitization. These results implicate GIRK channels as a therapeutic target for treating addiction, as well as other psychiatric disorders involving dopamine dysregulation.

GIRK currents in VTA dopamine neurons control the sensitivity of mice to cocaine-induced locomotor sensitization