Identification of a Novel N‐Methyl‐D‐Aspartate Receptor Population in the Rat Medial Thalamus

J. A. Beaton, K. Stemsrud, D. T. Monaghan

Research output: Contribution to journalArticle

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Abstract

Abstract: To evaluate the possibility of pharmacologically distinct N‐methyl‐D‐aspartate (NMDA) receptor subtypes, quantitative autoradiography was used to determine the potency of several compounds as inhibitors of l‐[3H]glutamate or [3H]MK‐801 binding to rat brain NMDA receptors in 10 brain regions. Competitive NMDA receptor antagonists displayed differing pharmacological profiles in the forebrain, cerebellum, and medial regions of the thalamus (midline nuclei). For example, compared with other competitive antagonists, 3‐[(±)‐2‐carboxypiperazin‐4‐yl]propyl‐1‐phosphonate (CPP) and LY‐233536 were especially weak displacers of l‐[3H]glutamate binding in the cerebellum. In the medial thalamus, CPP and D‐2‐amino‐5‐phosphonopentanoate displayed relatively low affinities, whereas LY‐233536 was relatively potent. The noncompetitive NMDA receptor antagonists also displayed regional variations in their pharmacological profiles. Relative to other regions, [3H]MK‐801 binding in the cerebellum was weakly displaced by MK‐801 and potently displaced by dextromethorphan and SKF‐10047. In the medial thalamus, 1‐[1‐(2‐thienyl)‐cyclohexyl]piperidine was relatively potent and SKF‐10047 was relatively weak. These results confirm previous suggestions that the cerebellum contains a distinct NMDA receptor subtype and indicate that nuclei of the medial thalamus contain a novel NMDA receptor subtype that is distinct from both those found in the cerebellum and in the forebrain.

Original languageEnglish (US)
Pages (from-to)754-757
Number of pages4
JournalJournal of Neurochemistry
Volume59
Issue number2
DOIs
Publication statusPublished - Aug 1992

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Keywords

  • Autoradiography
  • Glutamate receptors
  • MK‐801
  • N‐Methyl‐D‐aspartate receptors
  • Receptor isoforms

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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