REDUCTION OF SENSORY AND METABOTROPIC GLUTAMATE-RECEPTOR RESPONSES INTHE THALAMUS BY THE NOVEL METABOTROPIC GLUTAMATE RECEPTOR-1-SELECTIVEANTAGONIST S-2-METHYL-4-CARBOXY-PHENYLGLYCINE

Previous work has shown that responses of thalamic neurons in vivo to the metabotropic glutamate receptor agonists 1S,3R-aminocyclopentane-1 ,3-dicarboxylate and S-3,5-dihydroxyphenylglycine can be reduced by a variety of phenylglycine antagonists.(5,22,23). Responses of thalamic neurons to noxious thermal somatosensory stimuli were reduced in paral lel by these antagonists,(5,22) indicating that these responses are me diated by Group I metabotropic glutamate receptors (i.e. metabotropic glutamate receptor-1 and/or metabotropic glutamate receptor-5), which are known to be linked to phosphoinositol phosphate hydrolysis.(10,15, 18) The recent development of S-2-methyl-4-carboxy-phenylglycine as an antagonist which is highly selective for metabotropic glutamate recep tor-1 compared to metabotropic glutamate receptor-5 on human receptors expressed in AV-12 cells,(4) now offers the possibility of discrimina ting between these two receptor subtypes in order to distinguish which is involved in thalamic responses. We have made recordings from singl e somatosensory neurons in the thalamus of the rat, and find that S-2- methyl-3-carboxy-phenylglycine is able to reduce responses of neurons to 1S,3R-aminocyclopentane-1,3-dicarboxylate, S-3,5-dihydroxyphenylgly cine, and noxious stimuli without significant effect on responses to e ither N-methyl-D-aspartate or ha-amino-3-hydroxy-5-methyl-4-isoxazolep ropionate. These results suggest that excitatory responses of thalamic neurons to 1S,3R-aminocyclopentane-1,3-dicarboxylate and S-3,5-dihydr oxyphenylglycine may be mediated by metabotropic glutamate receptor-1. Furthermore, the reduction of nociceptive responses by S-2-methyl-4-c arboxy-phenylglycine indicates that metabotropic glutamate receptor-1 is involved in thalamic nociceptive processing and that such antagonis ts may have analgesic properties. (C) 1998 IBRO. Published by Elsevier Science Ltd.