Distinctions between persistent and reversible group I mGluR-induced epileptiform burst prolongation.

We have previously shown that selective activation of group I metabotropic glutamate receptors (mGluRs) results in long-lasting enhancement of synchronized network activity in the hippocampal slice. Data herein suggest that activation of group I mGluRs need not result in this potentially epileptogenic effect. (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (ACPD), a nonselective mGluR agonist, elicits ictaform bursts identical in appearance to those induced by selective agonists, but ACPD-induced bursts do not persist following removal of the agent. Like the bursts induced by selective agonist, the ACPD bursts are blocked with group I mGluR antagonists and are not dependent on activation of either N-methyl-D-aspartate (NMDA) receptors or protein kinase C. However, they differ from the persistent bursts in that they do not require active protein synthesis and they are not suppressed with L-cysteine sulfinic acid, an agonist at a phospholipase D-coupled metabotropic receptor. These novel findings provide evidence that group I mGluR-induced epileptogenesis may be preventable.