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

TY - JOUR

T1 - Activation of group I mGluRs potentiates NMDA responses in rat hippocampal slices

AU - Fitzjohn, Stephen M.

AU - Irving, Andy J.

AU - Palmer, Mary J.

AU - Harvey, Jenni

AU - Lodge, David

AU - Collingridge, Graham L.

PY - 1996/1/26

Y1 - 1996/1/26

N2 - 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.

AB - 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.

KW - (RS)-3,5-Dihydroxyphenylglycine

KW - Glutamate

KW - Hippocampus

KW - Metabotropic glutamate receptor

KW - N-Methyl-D-aspartate

UR - https://www.scopus.com/pages/publications/0030045961

U2 - 10.1016/0304-3940(96)12301-6

DO - 10.1016/0304-3940(96)12301-6

M3 - Article

C2 - 8742030

AN - SCOPUS:0030045961

SN - 0304-3940

VL - 203

SP - 211

EP - 213

JO - Neuroscience Letters

JF - Neuroscience Letters

IS - 3

ER -