(R)-4-Carboxyphenylglycine

(R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) fails to block long-term potentiation under urethane anaesthesia in vivo.[Pubmed:9423922]

Neuropharmacology. 1997 Oct;36(10):1339-54.

The effects of the metabotropic glutamate receptor antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) on the induction of long-term potentiation (LTP) in the dentate gyrus were examined under urethane anaesthesia in vivo. In experiment 1, bilateral intraventricular infusion of either 20 mM or 200 mM (R,S)-MCPG (5 microl each side) failed to block LTP in the perforant path-granule cell projection, relative to vehicle-infused controls; 30 mM D-AP5 (5 microl each side) infused in the same way as MCPG completely blocked LTP. Experiment 2, in which the contralateral perforant path-dentate gyrus pathway was used as a non-tetanized control, revealed that slight baseline changes induced by MCPG infusion were transient; again no block of LTP was obtained. The efficacy of mGluR blockade was confirmed in experiment 3, in which MCPG antagonized an increase in spontaneous activity induced by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD). In experiment 4, significant depotentiation was induced by low frequency stimulation (5 Hz for 1 min) given 2 min after high frequency tetanization, but MCPG remained ineffective in blocking LTP after a second tetanus. In experiment 5, increasing the period of low frequency stimulation from 1 to 10 min produced greater depotentiation, but still did not unmask an MCPG-sensitive component of LTP. These experiments fail to support a role for mGluRs in the induction of LTP in the dentate gyrus under urethane anaesthesia in vivo, nor do they support the idea that a metabotropic switch controlling sensitivity to MCPG is reset by depotentiation.

(R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) blocks spatial learning in rats and long-term potentiation in the dentate gyrus in vivo.[Pubmed:8177513]

Neurosci Lett. 1994 Feb 14;167(1-2):141-4.

Recently, it was demonstrated by the use of the competitive and selective antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) that metabotropic glutamate receptor (mGluR) activation is required to induce long-term potentiation (LTP) in the hippocampus. Accordingly, we investigated whether MCPG also inhibits spatial learning. Rats were trained on a spatial alternation task in a Y-maze with footshock reinforcement, and MCPG (0.0208 mg) was injected intracerebroventricularly prior to training and/or retention test. Animals injected pre-training are clearly impaired in retention, whereas preretention application was without effect. A state dependency could be excluded. Additionally, MCPG at the same concentration completely blocks a potentiation at perforant path/dentate gyrus synapses in vivo. These results strongly implicate a role of mGluRs in spatial learning and LTP.