title: The modulatory effect of CA1 GABAb receptors on ketamine-induced spatial and non-spatial novelty detection deficits with respect to Ca(2+).
abstract: Glutamate and γ-aminobutyric acid (GABA) are among the most abundant neurotransmitters in the central nervous system. Ketamine and other noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists are known to induce deficits in learning and the performance of cognitive tasks. The present study was designed to assess the effects of dorsal hippocampal (CA1) GABAb receptors on ketamine-induced spatial and non-spatial memory deficits with regard to the role of Ca(2+) as a defining factor. Spatial and non-spatial novelty detection of male NMRI mice were investigated in a circular open-field apparatus. According to our results, the intraperitoneal injection of ketamine at its higher dose (0.1 mg/kg) impaired both spatial and non-spatial novelty detection. Moreover, the intra-CA1 injection of baclofen (a GABAb receptor agonist) at higher doses (0.02 and 0.2 μg/mouse) impaired the spatial but not non-spatial novelty detection. In addition, phaclofen (a GABAb receptor antagonist at 0.2 μg/mouse) impaired both spatial and non-spatial novelty detection. Baclofen restored and induced a modulatory effect on ketamine-induced responses in the spatial and non-spatial novelty detection task, respectively. On the contrary, phaclofen restored and induced a modulatory effect on ketamine-induced responses in the non-spatial and spatial novelty detection task, respectively. Finally, the subthreshold dose of SKF96365 (a Ca(2+) channel blocker) impaired only the spatial but not non-spatial restoration effects of baclofen or phaclofen following a higher dose of ketamine. Such findings suggest that the ketamine-induced impairment of memory consolidation may occur through GABAb receptors of the CA1 neurons. Moreover, baclofen and phaclofen were shown to possibly exert their effects on the ketamine-induced spatial novelty detection deficits through Ca(2+) channels.
authors.affiliation: Institute for Cognitive Science Studies (ICSS), Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Khanegheini
authors.affiliation: Institute for Cognitive Science Studies (ICSS), Tehran, Iran; Cognitive and Neuroscience Research Center (CNRC), Medical Genomics Research Center and School of Advanced Sciences in Medicine, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran. Electronic address: Nasehi@iricss.org.
authors.forename: M
authors.initials: M
authors.lastname: Nasehi
authors.affiliation: Institute for Cognitive Science Studies (ICSS), Tehran, Iran; Cognitive and Neuroscience Research Center (CNRC), Medical Genomics Research Center and School of Advanced Sciences in Medicine, Islamic Azad University, Tehran Medical Sciences Branch, 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. Electronic address: zarinmr@ams.ac.ir.
authors.forename: M-R
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007649:Ketamine / Q000633:toxicity*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000473:pathology; D051379:Mice; D011963:Receptors, GABA-A / Q000378:metabolism*; D017603:Signal Detection, Psychological / Q000187:drug effects; D065855:Spatial Processing / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007093:Imidazoles; D011963:Receptors, GABA-A; C052329:phaclofen; D007649:Ketamine; D001418:Baclofen; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium
keywords: CA1; GABAb; ketamine; spatial memory