Group I metabotropic glutamate receptors modulate glutamate and γ-aminobutyric acid release in the periaqueductal grey of rats

Abstract

In this study, we investigated the effects of group I metabotropic glutamate (mglu) receptor ligands on glutamate and γ-aminobutyric acid (GABA) extracellular concentrations at the periaqueductal grey level by using in vivo microdialysis. An agonist of group I mglu receptors, ( S)-3,5-dihydroxyphenylglycine [( S)-3,5-DHPG, 1 and 2 mM], as well as a selective agonist of mglu 5 receptors, ( RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 2 and 4 mM), both increased dialysate glutamate and GABA concentrations. 7-(Hydroxyimino)cyclopropa-[ b]-chromen-1α-carboxylate ethyl ester (CPCCOEt, 1 mM), a selective mglu 1 receptor antagonist, and 2-methyl-6-(phenylethynyl)pyridine (MPEP, 0.5 mM), a selective mglu 5 receptor antagonist, perfused in combination with DHPG, antagonized the effect induced by DHPG on the extracellular glutamate and GABA concentrations. MPEP (0.5 mM), perfused in combination with CHPG, antagonized the increased glutamate and GABA extracellular levels induced by CHPG. MPEP (1 mM) decreased the extracellular concentrations of glutamate but did not modify the dialysate GABA concentrations. Moreover, as the intra-periaqueductal grey perfusion of ( RS)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid [( RS)-CPP, 100 μM], a selective N-methyl- d-aspartate (NMDA) glutamate receptor antagonist, did not change the extracellular concentrations of glutamate, this suggests that the MPEP-induced decrease in glutamate is not a consequence of NMDA receptor blockade. These data show that group I mglu receptors in the periaqueductal grey may modulate the release of glutamate and GABA in awake, freely moving rats. In particular, mglu 5, but not mglu 1, receptors seem to be functionally active on glutamate terminals.