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) 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.