A role for the GIRK3 subunit in methamphetamine-induced attenuation of GABAb receptor-activated GIRK currents in vta dopamine neurons

Michaelanne B. Munoz, Robert Rifkin, Claire L. Padgett, Kevin Wickman, Candice Contet, Stephen J. Moss, Paul A. Slesinger

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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 GABAB receptor (GABABR)-activated GIRK currents (IBaclofen) 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 GABABR-GIRK currents in VTA DA neurons required activation of both D1R-like and D2R-like receptors. The methamphetamine-dependent decrease in GABABR-GIRK currents in VTA DA neurons did not depend on a mechanism of dephosphorylation of the GABAB 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 GABABR-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.

Original languageEnglish (US)
Pages (from-to)3106-3114
Number of pages9
JournalJournal of Neuroscience
Volume36
Issue number11
DOIs
StatePublished - Mar 16 2016

Bibliographical note

Publisher Copyright:
© 2016 Ezcurra et al.

Keywords

  • Addiction
  • PDZ
  • Plasticity
  • Potassium channel
  • Psychostimulants
  • Reward

Fingerprint Dive into the research topics of 'A role for the GIRK3 subunit in methamphetamine-induced attenuation of GABA<sub>b</sub> receptor-activated GIRK currents in vta dopamine neurons'. Together they form a unique fingerprint.

Cite this