DEPRESSION-LIKE EFFECTS OF LEVETIRACETAM WAS HALTED BY PRETREATMENT WITH N-METHYL-D-ASPARTATE RECEPTOR (NMDAR) BLOCKERS IN MICE

Document Type : Original Article

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Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

N-methyl-D-aspartate receptor (NMDAR) stimulation might be responsible for levetiracetam -(Lev) induced depression. The aim of our study is to evaluate the effect of noncompetitive NMDAR blockers, dextromethorphan (Dxt) and dizocilpine (MK801), on Lev- induced depression in mice. Male NMRI mice were daily injected with Lev for 14 days. Pretreatments with Dxt, or MK801 were performed 30 min prior to Lev administration. The locomotor test and the forced swimming test (FST) and the novelty suppressed feeding test (NSFT) were performed. Following Dxt or MK801 pretreatment immobility time during FST was lower than Lev alone. There was no change in the locomotor activity. During NSFT, Lev increased latency, and decreased food intake; while, pretreatment with Dxt or MK801 reversed these effects. To our knowledge this is the first study showing that NMDAR blockers prevented the depressive-like behavior induced by Lev in mice. And proved that, at least in part activation of NMDAR is responsible for Lev induced depression, that warrants further research.

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