The pharmacology of the metabotropic glutamate receptor (mGluR)-mediated 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 μM) potentiated responses to NMDA (15-25 μM), giving a dose ratio of 0.84 ± 0.02. The mGluR group I specific agonist (RS3,5-dihydroxyphenylglycine (DHPG) (3-10 μM) also induced a dose-dependent and reversible enhancement of responses to NMDA (dose ratio for 10 μM DHPG was 0.77 ± 0.02). In contrast, the group II selective agonist (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV; 0.5-1 μM) and the group III specific agonist (S)-2-amino-4-phosphonobutanoate (L-AP4; 50 μM) caused little or no potentiation of responses to NMDA. The potentiation induced by 3-5 μM DHPG was reversibly antagonised by the group I and II antagonist (+)-α-methyl-4-carboxyphenylglycine ((+)-MCPG; 1 mM). The present findings demonstrate that activation of group I mGluRs enhance NMDA responses in the hippocampus.
- Metabotropic glutamate receptor