title: Additive effect of harmane and muscimol for memory consolidation impairment in inhibitory avoidance task.
abstract: In the current study, we examined the effect of bilateral intra-dorsal hippocampal (intra-CA1) microinjections of GABAAreceptor agents on amnesia induced by a β-carboline alkaloid, harmane in mice. We used a single-trial step-down passive avoidance task to assess memory retention and then, open-field test to assess locomotor activity. The results indicated that post-training intra-CA1 injections of bicuculline - a GABAAreceptor antagonist - had no significant effect, while muscimol (0.01 and 0.1μg/mouse) - a GABAAreceptor agonist - impaired memory consolidation. Post-training intra-peritoneal (i.p.) infusion of harmane (3 and 5mg/kg) decreased memory consolidation. Furthermore, post-training intra-CA1 administration of sub-threshold dose of bicuculline (0.001μg/mouse) restored, whereas muscimol (0.001μg/mouse) potentiated impairment of memory consolidation induced by harmane. The isobologram analysis revealed that there is an additive effect between harmane and muscimol on impairment of memory consolidation. Moreover, all above doses of drugs did not alter locomotor activity. These findings suggest that GABAAreceptors of the CA1 area, at least partly, play a role in modulating the effect of harmane on memory consolidation.
authors.affiliation: Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. Electronic address: Nasehi@iricss.org.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Nasehi
authors.affiliation: Department of Biology, Faculty of Basic Sciences, Kharazmi (Tarbiat Moalem) University, Tehran, Iran.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Morteza-Zadeh
authors.affiliation: Institute for Cognitive Science Studies (ICSS), Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Khakpai
authors.affiliation: Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran; Institute for Cognitive Science Studies (ICSS), 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; Medical Genomics Research Center, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. Electronic address: Zarinmr@ams.ac.ir.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D018697:Nootropic Agents; D011963:Receptors, GABA-A; D009118:Muscimol; D006247:Harmine; C005010:harman
keywords: GABA(A) receptor; harmane; memory; step-down passive avoidance; the CA1 area