Dopaminergic and GABAergic modulation of glutamate release from rat subthalamic nucleus efferents to the substantia nigra

Theo Hatzipetros, Bryan K. Yamamoto

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The regulation of the glutamatergic projection from the subthalamic nucleus (STN) to the substantia nigra (SN) was investigated using dual-probe microdialysis in the awake behaving rat. Reverse dialysis of the cholinergic receptor agonist carbachol (1 mM) into the STN caused an increase in the extracellular concentrations of glutamate and dopamine in the SN. The increase in glutamate was transient and returned toward basal values despite the continued perfusions of the STN with carbachol. Carbachol-stimulated glutamate release was prolonged by perfusion of the selective D2 dopamine receptor antagonist raclopride (100 μM) into the SN and was attenuated by the perfusion of the selective D2-like receptor agonist quinpirole (10 μM). In contrast, perfusion of the D1 dopamine receptor antagonist SCH-23390 (100 μM) did not alter the carbachol-stimulated glutamate release even though it increased basal glutamate concentrations. Perfusion of the GABAA receptor antagonist bicuculline (10 μM) into the SN prolonged the carbachol-stimulated glutamate release in similar fashion as raclopride. The present findings suggest that somatodendritically released dopamine in the SN regulates glutamate release from subthalamic axon terminals by differentially activating dopamine D2 and D1 receptors. Activation of D2 heteroreceptors, located on STN axon terminals, provides a negative feedback control on stimulated subthalamic glutamate release, while D1 receptor activation preferentially regulates basal glutamate concentrations. The findings of the present study also indicate that GABA exerts an inhibitory control on glutamate release in the SN through GABAA receptors.

Original languageEnglish (US)
Pages (from-to)60-67
Number of pages8
JournalBrain research
Volume1076
Issue number1
DOIs
StatePublished - Mar 3 2006
Externally publishedYes

Keywords

  • Dopamine
  • GABA
  • Glutamate
  • Parkinson's disease
  • Substantia nigra
  • Subthalamic nucleus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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