INTRACEREBRAL 1S,3R-1-AMINOCYCLOPENTANE-1,3-DICARBOXYLIC ACID (1S,3R-ACPD) PRODUCES LIMBIC SEIZURES THAT ARE NOT BLOCKED BY IONOTROPIC GLUTAMATE-RECEPTOR ANTAGONISTS

The functional role of metabotropic glutamate receptor (mGluR) activat ion was investigated following intracerebral administration of 1S,3R-A CPD in mice. Injections of 1S,3R-ACPD (50-800 nmol in 5 mul) 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 mG luR partial agonist/antagonist L-2-amino-3-phosphonopropionate (L-AP3) and dantrolene, an inhibitor of intracellular calcium mobilization, b ut not by D-AP3 or ionotropic glutamate receptor antagonists (MK-801 o r GYKI-52466). Thus, activation of mGluRs by 1S,3R-ACPD in mice, induc es limbic seizures that may involve the mobilization of intracellular calcium stores.