Cocaine Decreases Metabotropic Glutamate Receptor mGluR1 Currents in Dopamine Neurons by Activating mGluR5

Paul F. Kramer, John T. Williams

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Midbrain dopamine neurons are important mediators of reward and movement and are sensitive to cocaine-induced plasticity. After even a single injection of cocaine, there is an increase in AMPA-dependent synaptic transmission. The present study examines cocaine-induced plasticity of mGluR-dependent currents in dopamine neurons in the substantia nigra. Activation of mGluR1 and mGluR5 resulted in a mixture of inward and outward currents mediated by a nonselective cation conductance and a calcium-activated potassium conductance (SK), respectively. A single injection of cocaine decreased the current activated by mGluR1 in dopamine neurons, and it had no effect on the size of the mGluR5-mediated current. When the injection of cocaine was preceded by treatment of the animals with a blocker of mGluR5 receptors (MPEP), cocaine no longer decreased the mGluR1 current. Thus, the activation of mGluR5 was required for the cocaine-mediated suppression of mGluR1-mediated currents in dopamine neurons. The results support the hypothesis that mGluR5 coordinates a reduction in mGluR1 functional activity after cocaine treatment.

Original languageEnglish (US)
Pages (from-to)2418-2424
Number of pages7
JournalNeuropsychopharmacology
Volume40
Issue number10
DOIs
StatePublished - Sep 14 2015

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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