ACTIVATION OF GROUP-I MGLURS POTENTIATES NMDA RESPONSES IN RAT HIPPOCAMPAL SLICES

The pharmacology of the metabotropic glutamate receptor (mGluR)-mediat ed potentiation of N-methyl-D-aspartate (NMDA)-evoked depolarisations in the CA1 region of rat hippocampal slices was investigated using an extracellular grease-gap method. The group I and II mGluR agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD; 10 mu M) potentiated responses to NMDA (15-25 mu M), giving a dose ratio of 0.8 4 +/- 0.02. The mGluR group I specific agonist (RS3,5-dihydroxyphenylg lycine (DHPG) (3-10 mu M) also induced a dose-dependent and reversible enhancement of responses to NMDA (dose ratio for 10 mu M DHPG was 0.7 7 +/- 0.02). In contrast, the group II selective agonist 1'R,2'R,3'R)- 2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV; 0.5-1 mu M) and the gro up III specific agonist (S)-2-amino-4-phosphonobutanoate (L-AP4; 50 mu M) caused little or no potentiation of responses to NMDA. The potenti ation induced by 3-5 mu M DHPG was reversibly antagonised by the group I and II antagonist (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG ; 1 mM). The present findings demonstrate that activation of group I m GluRs enhance NMDA responses in the hippocampus.