title: The involvement of dorsal hippocampus in dextromethorphan-induced state-dependent learning in mice.
abstract: In an effort to understand the effect of dextromethorphan (DM; 3-methoxy-17-methylmorphinan), a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptors on memory retrieval, male NMRI mice received intraperitoneal (i.p.) or intra-CA1 injection of this drug before or after training and before testing in passive avoidance task. Pre-training i.p. (20mg/kg) or intra-CA1 (0.5 and 1 μg/mouse) administration of DM induced amnesia in a dose-dependent manner. Post-training i.p. (10 and 20mg/kg) or intra-CA administration of DM (0.5 and 1 μg/mouse) however, did not affect the memory retrieval. Moreover, memory retrieval was impaired in animals receiving either i.p. (20mg/kg) or intra-CA1 administration of DM (0.5 and 1 μg/mouse) prior to testing, suggesting the DM-induced amnesia. Interestingly, the amnestic effect of pre-training i.p. (20mg/kg) or intra-CA1 administration of DM (1 μg/mouse) was restored in mice receiving pre-test i.p. (5 and 10mg/kg) or intra-CA1 (0.25 and 0.5 μg/mouse) administration of the drug, indicating DM-induced state-dependent learning. Taken together, it can be concluded that DM administration impairs memory retrieval in a dose- and time-dependent manner. Moreover, DM can induce state-dependent learning. Dorsal hippocampus appears to play an important role upon DM influence of learning and memory processes.
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran; Institute of Cognitive Science Studies (ICSS), Tehran, Iran. Electronic address: zarinmr@ams.ac.ir.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Ownegh
authors.affiliation: Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Ameneh
authors.initials: A
authors.lastname: Rezayof
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farid
authors.initials: F
authors.lastname: Ownegh
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000502:physiology; D003915:Dextromethorphan / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice
chemical_list: D003915:Dextromethorphan
keywords: Dextromethorphan; Dorsal hippocampus; Mice; Passive avoidance learning