Activation of group I mGluRs potentiates NMDA responses in rat hippocampal slices.
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 mu M) potentiated responses to NMDA (15-25 mu M), giving a dose ratio of 0.84 +/- 0.02. The mGluR group I specific agonist (RS3,5-dihydroxyphenylglycine (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 0.77 +/- 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 mu M) and the group III specific agonist (S)-2-amino-4-phosphonobutanoate (L-AP4; 50 mu M) caused little or no potentiation of responses to NMDA. The potentiation 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 mGluRs enhance NMDA responses in the hippocampus.
Fitzjohn
S M
SM
Department of Anatomy, School of Medical Sciences, University of Bristol, Birmingham, UK.
Irving
A J
AJ
Palmer
M J
MJ
Harvey
J
J
Lodge
D
D
Collingridge
G L
GL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*
D018094:Receptors, Metabotropic Glutamate; D016202:N-Methylaspartate