PRESYNAPTIC MGLU(1) TYPE RECEPTORS POTENTIATE TRANSMITTER OUTPUT IN THE RAT CORTEX

In the present study we used freely moving rats with a microdialysis p robe placed in their parietal cortex to study the effects of local app lication of agonists and antagonists of metabotropic glutamate (mGlu) receptors on glutamate release. (1S,3R)-1-aminocyclopentane-1,3-dicarb oxylic acid (1S,3R-ACPD; 0.1-1 mM), a non-selective agonist of metabot ropic glutamate (mGlu) receptors, increased glutamate concentration in the dialysate up to 3-fold. A significant increase in glutamate outpu t in cortical dialysates was also obtained with (RS)-3,5-dihydroxyphen ylglycine (DHPG; 0.5-1 mM), a group 1-selective mGlu receptor agonist, suggesting the involvement of group 1 mGlu receptors in 1S,3R-ACPD ef fects. S-4-carboxyphenylglycine (S-4CPG; 0.3 mu M), a mGlu(1) receptor antagonist with a mild agonist action on mGlu(2) receptors, antagonis ed, in a surmountable manner, the effects of 1S,3R-ACPD. Similarly, 1- aminoindan-1,5-dicarboxylic acid (AIDA; 0.03-1 mM) a selective group 1 antagonist with a preferential action on mGlu(1) type receptors, anta gonised the effects of 1S,3R-ACPD. Finally, (S)-(+)-2-(3'-Carboxybicyc lo[1.1.1]pentyl)-glycine (UPF596; 30-300 mu M), a potent mGlu(1) antag onist with modest agonist activity on mGlu(5), antagonised 1S,3R-ACPD- induced glutamate release. In conclusion, our data showed that 1S,3R-A CPD-induced glutamate release in the parietal cortex is mediated by mG lu(1) receptors and that, under basal conditions, these receptors are not tonically activated. (C) 1998 Elsevier Science B.V.