METABOTROPIC GLUTAMATE-RECEPTOR ACTIVATION DECREASES EPILEPTIFORM ACTIVITY IN RAT NEOCORTEX

Intracellular and extracellular recordings were obtained from layers II-III of slices of adult rat neocortex maintained in vitro. Excitatory postsynaptic potentials (EPSPs) and epileptiform discharges (paroxysmal depolarizing shifts, PDSs) were evoked in the presence of bicuculline methiodide. Responses were monitored before, during, and after bath application of the putative metabotropic glutamate receptor agonists, 1S,3R-ACPD and L-AP4. Peak EPSP amplitude and both PDS amplitude and duration were reduced during 1S,3R-ACPD application. Area measurements indicate that PDSs were reduced to 51.7 +/- 19.9% of control. Stimulus threshold for evoking a PDS was increased in the presence of 1S,3R-ACPD or L-AP4. Pretreatment of slices with 1S,3R-ACPD did not prevent the generation of epileptiform events when bicuculline subsequently was applied. These results indicate that mGluR activation by 1S,3R-ACPD has significant suppressive effects on evoked epileptiform activity in the adult rat neocortex in vitro.