Effect of CGP 36742 on the extracellular level of neurotransmitter amino acids in the thalamus

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Abstract

We have evaluated the effect of the brain penetrating GABAb antagonist, CGP 36742 on GABAb receptors using in vivo microdialysis in the ventrobasal thalamus of freely moving rat. When a solution of 1mM CGP 36742 in ACSF was dialyzed into the ventrobasal thalamus, 2-3-fold increases of extracellular Glu, Asp and Gly running parallel with significant decreases of contralateral extracellular Asp and Gly were observed. Unilateral applications of Glu receptor antagonists (0.5 mM MK801, 0.1 mM CNQX) evoked 2-3-fold decreases of CGP 36742-specific elevations of extracellular Asp, Glu and Gly. Administration of CNQX and MK801 in the absence of CGP 36742 did not alter the extracellular Glu and Gly concentrations whereas extracellular Asp concentrations diminished by 42-45% at both sides. By contrast, no changes of extracellular Gly accompanied the 5-10-fold enhancements of extracellular Asp and Glu, observed during application of the Glu uptake inhibitor, tPDC (1mM). Suspensions of resealed plasmalemma fragments from the rat thalamus were mixed rapidly with the membrane impermeant form of the fluorescence indicator, bis-fura-2 and the changes in fluorescence intensity in response to CGP 36742 (0.5 mM), and the GABAb agonist, baclofen (0.1mM), were monitored on the time scale of 0.04 ms-10 s. Progress of CGP 36742-mediated influx, and baclofen-mediated efflux of Ca++ ion, antagonized by CGP 36742, was observed in the 1 ms-10 s period of time. These data support the hypothesis that background ventrobasal activities and thalamocortical signaling are under the control of inhibitory GABAb receptors in the ventrobasal thalamus. Copyright (C) 1999 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)391-398
Number of pages8
JournalNeurochemistry international
Volume34
Issue number5
DOIs
Publication statusPublished - máj. 1 1999

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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