Differential Roles for mGluR1 and mGluR5 in the Persistent Prolongation of Epileptiform Bursts Merlin LR J Neurophysiol 2002;87:621–625 Purpose Transient activation of group I metabotropic glutamate receptors (mGluRs) with the selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) produces persistent prolongation of epileptiform bursts in guinea-pig hippocampal slices, the maintenance of which can be reversibly suppressed with group I mGluR antagonists. To determine the relative roles of mGluR1 and mGluR5 in these group I mGluR-dependent induction and maintenance processes, subtype-selective antagonists were used. In the presence of picrotoxin, DHPG (50 μ M, 20–45 min) converted interictal bursts into 1- to 3-s discharges that persisted for hours after washout of the mGluR agonist. 2-Methyl-6–(phenylethynyl)-pyridine (MPEP, an mGluR5 antagonist; 25 μ M) and (+)-2-methyl-4-carboxy-phenylglycine (LY367385, an mGluR1 antagonist; 20–25 (μ M) each significantly suppressed the ongoing expression of the mGluR-induced prolonged bursts. However, LY367385 was more effective, reducing the burst prolongation by nearly 90%; MPEP produced only a 64% reduction in burst prolongation. Nevertheless, MPEP was more effective at preventing the induction of the burst prolongation; all 10 slices tested failed to express prolonged bursts both during and after coapplication of DHPG with MPEP. Coapplication of DHPG with LY367385, in contrast, resulted in significant burst prolongation (in 68% of slices tested) that was revealed on washout of the two agents. These results suggest that although both receptor subtypes participate in both the induction and maintenance of mGluR-mediated burst prolongation, mGluR1 activation plays a greater role in sustaining the expression of prolonged bursts, whereas mGluR5 activation may be a more critical contributor to the induction process underlying this type of epileptogenesis.