A Role for the GIRK3 Subunit in Methamphetamine-Induced Attenuation of GABA(B) Receptor-Activated GIRK Currents in VTA Dopamine Neurons

作者：Munoz Michaelanne B; Padgett Claire L; Rifkin Robert; Terunuma Miho; Wickman Kevin; Contet Candice; Moss Stephen J; Slesinger Paul A^*

来源：Journal of Neuroscience, 2016, 36(11): 3106-3114.

DOI：10.1523/JNEUROSCI.1327-15.2016

• addiction
• PDZ
• plasticity
• potassium channel
• psychostimulants
• reward

Repeated exposure to psychostimulants induces locomotor sensitization and leads to persistent changes in the circuitry of the mesocorticolimbic dopamine (DA) system. G-protein-gated inwardly rectifying potassium (GIRK; also known as Kir3) channels mediate a slow IPSC and control the excitability of DA neurons. Repeated 5 d exposure to psychostimulants decreases the size of the GABA(B) receptor (GABA(B)R)-activated GIRK currents (I-Baclofen) in ventral tegmental area (VTA) DA neurons of mice, but the mechanism underlying this plasticity is poorly understood. Here, we show that methamphetamine-dependent attenuation of GABA(B)R-GIRK currents in VTA DA neurons required activation of both D1R-like and D2R-like receptors. The methamphetamine-dependent decrease in GABA(B)R-GIRK currents in VTA DA neurons did not depend on a mechanism of dephosphorylation of the GABA(B) R2 subunit found previously for other neurons in the reward pathway. Rather, the presence of the GIRK3 subunit appeared critical for the methamphetamine-dependent decrease of GABA(B)R-GIRK current in VTA DA neurons. Together, these results highlight different regulatory mechanisms in the learning-evoked changes that occur in the VTA with repeated exposure to psychostimulants.

• 出版日期2016-3-16