Striatal dopamine-NMDA receptor interactions in the modulation of glutamate release in the substantia nigra pars reticulata in vivo: opposite role for D1 and D2 receptors

J Neurochem. 2002 Nov;83(3):635-44. doi: 10.1046/j.1471-4159.2002.01169.x.

Abstract

Dual probe microdialysis was employed in conscious rats to investigate whether endogenous dopamine is involved in the stimulation of glutamate release in the substantia nigra pars reticulata following striatal NMDA receptor activation. Intrastriatal perfusion with NMDA (1 and 10 microm) facilitated nigral glutamate release (dizocilpine- and tetrodotoxin-sensitive). The D2 dopamine receptor antagonist raclopride increased spontaneous nigral glutamate release and caused a leftward shift in the NMDA sensitivity, lowering NMDA effective concentrations to submicromolar levels. Conversely, the D1 antagonist SCH23390 prevented the effect of NMDA (1 microm) and caused a rightward shift in the NMDA sensitivity. It was tested whether the antagonist effects were due to dopamine receptor blockade or increased tone on D1/D2 receptors. SCH23390 prevented the raclopride-induced enhancement of spontaneous but not NMDA-evoked glutamate release while raclopride left unchanged the SCH23390-induced inhibition. The physiopathological relevance of the dopaminergic modulation was strengthened by perfusing NMDA in the dopamine-depleted striatum of hemiparkinsonian rats. Nigral glutamate responsiveness to NMDA was enhanced as with raclopride. We conclude that endogenous striatal dopamine regulates both spontaneous and NMDA-induced nigral glutamate release via an opposite control mediated by D1 facilitatory and D2 inhibitory receptors. Alterations of this control may subserve the motor symptoms of Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology
  • Dopamine D2 Receptor Antagonists
  • Glutamic Acid / metabolism*
  • Male
  • Microdialysis
  • N-Methylaspartate / pharmacology
  • Oxidopamine
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / metabolism
  • Perfusion
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Substantia Nigra / metabolism*
  • Wakefulness

Substances

  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • N-Methylaspartate
  • Oxidopamine
  • Dopamine