Non-competitive N-methyl-d-aspartate antagonists are potent activators of ventral tegmental A10 dopamine neurons

Edward D. French, Angelo Ceci

Research output: Contribution to journalArticle

155 Scopus citations

Abstract

The response of ventral tegmental (VTA) A10 dopamine neurons to a series of compounds covering the spectrum from high-affinity phencyclidine receptor ligands (MK-801, PCP) to high-affinity σ-receptor ligands ((+)-pentazocine, DTG) was measured using single-unit extracellular recording techniques in the rat. Dose-response comparisons revealed that MK-801 was 3, 6, 19 and 119 times more potent at activating A10 neurons than PCP, (+)-SKF-10,047, ketamine and (+)-pentazocine, respectively. DTG (1,3-di-o-tolylguanidine), the most selective σ-ligand, and U50,488H, a κ-opiate, failed to produce any stimulation of firing. Also, pretreatment with haloperidol, a potent σ-receptor ligand, did not prevent MK-801-induced excitations. Thus, the activation of the A10-mesolimbic-mesocortical dopamine pathways by PCP, PCP-like drugs and σ-psychotomimetics is mediated by the PCP receptor, not the haloperidol-sensitive σ-receptor, with potencies directly correlated to their activity as non-competitive N-methyl-d-aspartate (NMDA) antagonists.

Original languageEnglish (US)
Pages (from-to)159-162
Number of pages4
JournalNeuroscience Letters
Volume119
Issue number2
DOIs
StatePublished - Nov 13 1990

Keywords

  • A dopamine neuron
  • Electrophysiology
  • MK-801
  • PCP
  • σ-Benzomorphan

ASJC Scopus subject areas

  • Neuroscience(all)

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