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

ABSTRACT: GABA_BR-dependent activation of G protein-gated inwardly rectifying potassium channels (GIRK or K_IR3) provides a well-known source of inhibition in the brain, but the details on how this important inhibitory pathway affects neural circuits are lacking. We used sorting nexin 27 (SNX27), an endosomal adaptor protein that associates with GIRK2c and GIRK3 subunits, to probe the role of GIRK channels in reward circuits. A conditional knockout of SNX27 in both substantia nigra pars compacta and ventral tegmental area (VTA) dopamine neurons leads to markedly smaller GABA_BR- and dopamine D₂R-activated GIRK currents, as well as to suprasensitivity to cocaine-induced locomotor sensitization. Expression of the SNX27-insensitive GIRK2a subunit in SNX27-defici

SUBMITTER: Rifkin RA 

PROVIDER: S-EPMC6176583 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature