Neuroprotective effect caused by MPEP, an antagonist of metabotropic glutamate receptor mGluR5, on seizures induced by pilocarpine in 21-day-old rats

This study was designed to verify the influence of MPEP (2-methyl-6-phenylethynyl pyridine hydrochloride), an antagonist of metabotropic glutamate receptor subtype 5 (mGluR5), in seizures and status epilepticus (SE) induced by pilocarpine in young rats. In order to investigate the protective effect of MPEP on pilocarpine-induced seizures, young male rats (21-day-old) were pretreated by intraperitoneal route (i.p.) with MPEP (1, 5 and 15 mg/kg) before of pilocarpine administration (400 mg/kg, i.p.). The animals were observed for 1 h after injection of pilocarpine (except pilocarpine group) to determine: number of peripheral cholinergic signs, tremors, stereotyped movements, seizures, SE, latency to the first seizure and number of deaths. Pretreatment with MPEP, at all doses, delayed the onset for the first seizure episode induced by pilocarpine in rats. MPEP abolished the mortality rate caused by administration of pilocarpine in rats. Pretreatment with MPEP (5 and 15 mg/kg) protected against the levels of RS (reactive species), CAT (catalase) and glutathione S-transferase (GST) activities in brain of rats altered by pilocarpine administration. MPEP, at all doses, protected acetylcholinsterase (AChE) activity inhibited by pilocarpine administration in rats. The results suggest that anticonvulsant action of MPEP can be attributed to its mGlu5 receptor antagonism. Therefore, blockade of mGIu5 receptors might represent a novel target for the treatment of seizures in young rats. (c) 2008 Elsevier B.V. All rights reserved.