title: The role of CA3 GABAA receptors on anxiolytic-like behaviors and avoidance memory deficit induced by NMDA receptor antagonists.
abstract: Cognitive functions are influenced by memory and anxiety states. However, a non-linear relation has been shown between these two domains. The important role of the hippocampus in memory and emotional responses may link the pathogenesis of anxiety to memory-related GABAergic and glutamatergic processes in the hippocampus. To investigate the role of GABAA receptors in relation to blocking N-methyl-D-aspartate (NMDA) receptors in the CA3 region, and balancing the glutamatergic and GABAergic system activities as an approach for the management of related disorders, the elevated plus-maze test-retest paradigm was used to investigate the anxiolytic-like state on the test day and avoidance memory state on the retest day. The data showed that injection of D-AP5, the NMDA receptor antagonist, induced anxiolytic-like behavior and impaired avoidance memory. Injection of GABAA agonist (muscimol), but not the antagonist (bicuculline), induced avoidance memory impairment. Neither muscimol nor bicuculline altered anxiety-like behaviors. Muscimol pretreatment did not change D-AP5-induced anxiolytic-like behaviors but potentiated avoidance memory impairment. Bicuculline pretreatment blocked D-AP5-induced anxiolytic-like behaviors and contradicted its effect on avoidance memory. Our findings indicate that alteration of the CA3 GABAA receptor activity can effectively affect the anxiolytic-like behaviors and avoidance memory deficit induced by D-AP5.
authors.affiliation: Institute for Cognitive Science Studies (ICSS), Tehran, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Zarrabian
authors.affiliation: Institute for Cognitive Science Studies (ICSS), Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Farahizadeh
authors.affiliation: Cognitive and Neuroscience Research Center (CNRC), Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Nasehi
authors.affiliation: 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 zarinmr@ams.ac.ir.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000473:pathology; D001362:Avoidance Learning / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D056654:CA3 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000473:pathology; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol; D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline
keywords: D-AP5; GABAA; anxiety; elevated plus-maze; memory; rats