Intracerebral 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) produces limbic seizures that are not blocked by ionotropic glutamate receptor antagonists.

Abstract

The functional role of metabotropic glutamate receptor (mGluR) activation was investigated following intracerebral administration of 1S,3R-ACPD in mice. Injections of 1S,3R-ACPD (50-800 nmol in 5 microliters) into the thalamus produced a dose-dependent increase in limbic seizures. These effects were stereoselective since 1R,3S-ACPD, did not elicit seizure activity. Pharmacologically, limbic seizures were attenuated by the mGluR partial agonist/antagonist L-2-amino-3-phosphonopropionate (L-AP3) and dantrolene, an inhibitor of intracellular calcium mobilization, but not by D-AP3 or ionotropic glutamate receptor antagonists (MK-801 or GYKI-52466). Thus, activation of mGluRs by 1S,3R-ACPD in mice, induces limbic seizures that may involve the mobilization of intracellular calcium stores.

• Authors: J P Tizzano, K I Griffey, J A Johnson, A S Fix, D R Helton, D D Schoepp
• Journal: Neuroscience letters (Neurosci Lett) Vol. 162 Issue 1-2 Pg. 12-6 (Nov 12 1993) ISSN: 0304-3940 [Print] Ireland
• PMID: 8121613 (Publication Type: Journal Article)

Chemical References

• Anticonvulsants
• Receptors, Amino Acid
• Receptors, Metabotropic Glutamate
• Cycloleucine
• 1-amino-1,3-dicarboxycyclopentane

Topics

• Animals
• Anticonvulsants (pharmacology)
• Cycloleucine (administration & dosage, analogs & derivatives, pharmacology)
• Dose-Response Relationship, Drug
• Hippocampus (anatomy & histology)
• Injections
• Limbic System (physiology)
• Male
• Mice
• Receptors, Amino Acid (antagonists & inhibitors)
• Receptors, Metabotropic Glutamate (antagonists & inhibitors)
• Seizures (chemically induced, physiopathology)
• Signal Transduction (drug effects)
• Stereoisomerism
• Thalamus (anatomy & histology)