N-methyl-d-aspartic acid biphasically regulates the biochemical and electrophysiological response of A10 dopamine neurons in the ventral tegmental area: in vivo microdialysis and in vitro electrophysiological studies

Ting Wang, William T. O'Connor, Urban Ungerstedt, Edward D French

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The effects of local perfusion of the ventral tegmental area (VTA) with N-methyl-d-aspartic acid (NMDA) on extracellular dopamine concentrations in the nucleus accumbens were investigated by using in vivo microdialysis in halothane anaesthetized rats. The electrophysiological response of VTA dopamine neurons to NMDA were also assessed in an in vitro rat brain slice preparation. In both preparations NMDA elicited a biphasic response. Exposure of the VTA to low doses of NMDA (< 100 μM) elicited increases in dialysate dopamine levels in the nucleus accumbens and increases in the firing rate of VTA dopamine neurons. Larger doses (> 100 μM) resulted in profound reductions in both dopamine release in the accumbens and firing in the VTA. A strong correlation between the ability of NMDA to influence dopamine release in the accumbens and the firing rate in the VTA was observed. Perfusion with the non-competitive NMDA receptor antagonist PCP eliminated the NMDA-induced increases in extracellular dopamine in the accumbens. These data suggest that dopamine release in the accumbens and the firing rate of dopamine neurons can be both increased or decreased depending upon the magnitude of glutamatergic stimulation within the VTA.

Original languageEnglish (US)
Pages (from-to)255-262
Number of pages8
JournalBrain Research
Volume666
Issue number2
DOIs
StatePublished - Dec 15 1994

Fingerprint

Ventral Tegmental Area
Dopaminergic Neurons
antineoplaston A10
Microdialysis
Aspartic Acid
Dopamine
Perfusion
Nucleus Accumbens
Halothane
In Vitro Techniques
Brain

Keywords

  • Electrophysiology
  • Excitatory amino acid
  • Microdialysis
  • NMDA
  • Phenycyclidine

ASJC Scopus subject areas

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

Cite this

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title = "N-methyl-d-aspartic acid biphasically regulates the biochemical and electrophysiological response of A10 dopamine neurons in the ventral tegmental area: in vivo microdialysis and in vitro electrophysiological studies",
abstract = "The effects of local perfusion of the ventral tegmental area (VTA) with N-methyl-d-aspartic acid (NMDA) on extracellular dopamine concentrations in the nucleus accumbens were investigated by using in vivo microdialysis in halothane anaesthetized rats. The electrophysiological response of VTA dopamine neurons to NMDA were also assessed in an in vitro rat brain slice preparation. In both preparations NMDA elicited a biphasic response. Exposure of the VTA to low doses of NMDA (< 100 μM) elicited increases in dialysate dopamine levels in the nucleus accumbens and increases in the firing rate of VTA dopamine neurons. Larger doses (> 100 μM) resulted in profound reductions in both dopamine release in the accumbens and firing in the VTA. A strong correlation between the ability of NMDA to influence dopamine release in the accumbens and the firing rate in the VTA was observed. Perfusion with the non-competitive NMDA receptor antagonist PCP eliminated the NMDA-induced increases in extracellular dopamine in the accumbens. These data suggest that dopamine release in the accumbens and the firing rate of dopamine neurons can be both increased or decreased depending upon the magnitude of glutamatergic stimulation within the VTA.",
keywords = "Electrophysiology, Excitatory amino acid, Microdialysis, NMDA, Phenycyclidine",
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AU - Wang, Ting

AU - O'Connor, William T.

AU - Ungerstedt, Urban

AU - French, Edward D

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N2 - The effects of local perfusion of the ventral tegmental area (VTA) with N-methyl-d-aspartic acid (NMDA) on extracellular dopamine concentrations in the nucleus accumbens were investigated by using in vivo microdialysis in halothane anaesthetized rats. The electrophysiological response of VTA dopamine neurons to NMDA were also assessed in an in vitro rat brain slice preparation. In both preparations NMDA elicited a biphasic response. Exposure of the VTA to low doses of NMDA (< 100 μM) elicited increases in dialysate dopamine levels in the nucleus accumbens and increases in the firing rate of VTA dopamine neurons. Larger doses (> 100 μM) resulted in profound reductions in both dopamine release in the accumbens and firing in the VTA. A strong correlation between the ability of NMDA to influence dopamine release in the accumbens and the firing rate in the VTA was observed. Perfusion with the non-competitive NMDA receptor antagonist PCP eliminated the NMDA-induced increases in extracellular dopamine in the accumbens. These data suggest that dopamine release in the accumbens and the firing rate of dopamine neurons can be both increased or decreased depending upon the magnitude of glutamatergic stimulation within the VTA.

AB - The effects of local perfusion of the ventral tegmental area (VTA) with N-methyl-d-aspartic acid (NMDA) on extracellular dopamine concentrations in the nucleus accumbens were investigated by using in vivo microdialysis in halothane anaesthetized rats. The electrophysiological response of VTA dopamine neurons to NMDA were also assessed in an in vitro rat brain slice preparation. In both preparations NMDA elicited a biphasic response. Exposure of the VTA to low doses of NMDA (< 100 μM) elicited increases in dialysate dopamine levels in the nucleus accumbens and increases in the firing rate of VTA dopamine neurons. Larger doses (> 100 μM) resulted in profound reductions in both dopamine release in the accumbens and firing in the VTA. A strong correlation between the ability of NMDA to influence dopamine release in the accumbens and the firing rate in the VTA was observed. Perfusion with the non-competitive NMDA receptor antagonist PCP eliminated the NMDA-induced increases in extracellular dopamine in the accumbens. These data suggest that dopamine release in the accumbens and the firing rate of dopamine neurons can be both increased or decreased depending upon the magnitude of glutamatergic stimulation within the VTA.

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