(R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) fails to block long-term potentiation under urethane anaesthesia in vivo.
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.
Martin
S J
SJ
Centre for Neuroscience and Department of Pharmacology, University of Edinburgh, UK. stevem@tattoo.ed.ac.uk
Morris
R G
RG
D000704:Analysis of Variance; D000758:Anesthesia; D018686:Anesthetics, Intravenous; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D001831:Body Temperature; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000187:drug effects*; D013742:Tetanus / Q000378:metabolism; D013997:Time Factors; D014520:Urethane
D018686:Anesthetics, Intravenous; D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079694:alpha-methyl-4-carboxyphenylglycine; D014520:Urethane; D005998:Glycine