Activation of group I mG1uRs potentiates NMDA responses in rat hippocampal slices

• Published in: Neuroscience letters 1996, Vol.203 (3), p.211-213
• Main Authors: Fitzjohna, Stephen M., Irving, Andy J., Palmer, Mary J., Harvey, Jenni, Lodge, David, Collingridge, Graham L.
• Format: Article
• Language: English
• Subjects: ( RS)-3,5-Dihydroxyphenylglycine; Glutamate; Hippocampus; Metabotropic glutamate receptor; N-Methyl- d-aspartate
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/0304-3940(96)12301-6

The pharmacology of the metabotropic glutamate receptor (mG1uR)-mediated potentiation of N-methyl- d-aspartate (NMDA)-evoked depolarisations in the CAI region of rat hippocampal slices was investigated using an extracellular grease-gap method. The group I and II mG1uR agonist (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1 S,3 R)-ACPD; 1OμM) 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) (3–10μM) 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 (2 S,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 hippocampas.