Presynaptic mGlu₁ type receptors potentiate transmitter output in the rat cortex

In the present study we used freely moving rats with a microdialysis probe placed in their parietal cortex to study the effects of local application of agonists and antagonists of metabotropic glutamate (mGlu) receptors on glutamate release. (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 0.1-1 mM), a non-selective agonist of metabotropic glutamate (mGlu) receptors, increased glutamate concentration in the dialysate up to 3-fold. A significant increase in glutamate output in cortical dialysates was also obtained with (RS)-3,5-dihydroxyphenylglycine (DHPG; 0.5-1 mM), a group 1-selective mGlu receptor agonist, suggesting the involvement of group 1 mGlu receptors in 1S,3R-ACPD effects. S-4- carboxyphenylglycine (S-4CPG; 0.3 μM), a mGlu₁ receptor antagonist with a mild agonist action on mGlu₂ receptors, antagonised, in a surmountable manner, the effects of 1S,3 R-ACPD. Similarly, 1-aminoindan-1,5-dicarboxylic acid (AIDA; 0.03-1 mM) a selective group 1 antagonist with a preferential action on mGlu₁ type receptors, antagonised the effects of 1S,3 R-ACPD. Finally, (S)-(+)-2-(3'-Carboxybicyclo[1.1.1]pentyl)-glycine (UPF596; 30-300 μM), a potent mGlu₁ antagonist with modest agonist activity on mGlu₅, antagonised 1S,3R-ACPD-induced glutamate release. In conclusion, our data showed that 1S,3R-ACPD-induced glutamate release in the parietal cortex is mediated by mGlu₁ receptors and that, under basal conditions, these receptors are not tonically activated.