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

We have evaluated the effect of the brain penetrating GABAb antagonist, CGP 36742 on GABAb receptors using in vivo microdialysis in the ventrobasal th alamus of freely moving rat. When a solution of 1 mM 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 contralate ral 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-specifrc elevations of extracellular Asp, Glu and Gly. Admini stration of CNQX and MK801 in the absence of CGP 36742 did not alter the ex tracellular Glu and Gly concentrations whereas extracellular Asp concentrat ions diminished by 42-45% at both sides. By contrast, no changes of extrace llular Gly accompanied the 5-10-fold enhancements of extracellular Asp and Glu, observed during application of the Glu uptake inhibitor, tPDC (1 mM). Suspensions of resealed plasmalemma fragments from the rat thalamus were mi xed rapidly with the membrane impermeant form of the fluorescence indicator , bis-fura-2 and the changes in fluorescence intensity in response to CGP 3 6742 (0.5 mM), and the GABAb agonist, baclofen (0.1 mM), 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 observe d in the 1 ms-10 s period of time. These data support the hypothesis that b ackground ventrobasal activities and thalamocortical signaling are under th e control of inhibitory GABAb receptors in the ventrobasal thalamus. (C) 19 99 Elsevier Science Ltd. All rights reserved.