title: Recovery from ketamine-induced amnesia by blockade of GABA-A receptor in the medial prefrontal cortex of mice.
abstract: Ketamine and other noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists are known to induce deficits in learning and cognitive performance sensitive to prefrontal cortex (PFC) functions. The interaction of a glutamatergic and GABAergic systems is essential for many cognitive behaviors. In order to understand the effect of γ-aminobutyric acid (GABA)/glutamate interactions on learning and memory, we investigated the effects of intra medial prefrontal cortex (mPFC) injections of GABAergic agents on ketamine-induced amnesia using a one-trial passive avoidance task in mice. Pre-training systemic administration of ketamine (5, 10 and 15mg/kg, i.p.) dose-dependently decreased the memory acquisition of a one-trial passive avoidance task. Pre-training intra-mPFC injection of muscimol, GABAA receptor agonist (0.05, 0.1 and 0.2μg/mouse) and baclofen GABAB receptor agonist (0.05, 0.1, 0.5 and 1μg/mouse), impaired memory acquisition. However, co-pretreatment of different doses of muscimol and baclofen with a lower dose of ketamine (5mg/kg), which did not induce amnesia by itself, caused inhibition of memory formation. Our data showed that sole pre-training administration of bicuculline, GABA-A receptor antagonist and phaclofen GABA-B receptor antagonist into the mPFC, did not affect memory acquisition. In addition, the amnesia induced by pre-training ketamine (15mg/kg) was significantly decreased by the pretreatment of bicuculline (0.005, 0.1 and 0.5μg/mouse). It can be concluded that GABAergic system of the mPFC is involved in the ketamine-induced impairment of memory acquisition.
authors.affiliation: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Farahmandfar
authors.affiliation: Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; Department of Basic Sciences, Faculty of Veterinary Medicine, Islamic Azad University, Garmsar Branch, Semnan, Iran.
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Akbarabadi
authors.affiliation: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Bakhtazad
authors.affiliation: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran; 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; School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran. Electronic address: zarinmr@ams.ac.ir.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000647:Amnesia / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002408:Catheters, Indwelling; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D007649:Ketamine / Q000633:toxicity*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D011963:Receptors, GABA-A; C052329:phaclofen; D009118:Muscimol; D007649:Ketamine; D001418:Baclofen; D001640:Bicuculline
keywords: GABAergic system; ketamine; medial prefrontal cortex; mice; passive avoidance