Antagonism of the mGlu5 agonist 2-chloro-5-hydroxyphenylglycine by the novel selective mGlu5 antagonist 6-methyl-2(phenylethynyl)-pyridine (MPEP) in the thalamus

Our previous work has shown that Group I mGlu receptors participate in thal amic sensory processing in viva. However, unequivocal demonstration of mGlu 5 participation has not been possible due to the lack of specific ligands. We have therefore made a preliminary study of the in vivo actions of the ag onist (R,S)-2-Chloro-5-hydroxyphenylglycine [CHPG] and the novel mGlu5 anta gonist 6-methyl-2-(phenylethynyl)-pyridine [MPEP] in order to characterize their suitability for functional studies. Iontophoretically administered MP EP selectively antagonized excitatory responses of single rat thalamic neur ones to CHPG compared to the broad-spectrum mGlu agonist (1S,3R)-1-aminocyc lopentane-1,3-dicarboxylate. In contrast, the established mGlu1 and mGlu5 a ntagonist (S)-4-carboxyphenylglycine reduced responses to both agonists. Th ese findings are the first demonstration of an in vivo action of CHPG and i ts antagonism by a selective mGlu5 antagonist. Furthermore MPEP appears to be a good tool for functional studies of mGlu5.