title: Role of the amygdala GABA-A receptors in ACPA-induced deficits during conditioned fear learning.
abstract: The basolateral amygdala (BLA) is a key structure for the emotional processing and storage of memories associated with emotional events, especially fear. On the other hand, endocannabinoids and CB1 receptors play a key role in learning and memory partly through long-term synaptic depression of GABAergic synapses in the BLA. The aim of this study was to explore the effects of GABA-A receptor agonist and antagonist in the fear-related memory acquisition deficits induced by ACPA (a selective CB1 cannabinoid receptor agonist). This study used context and tone fear conditioning paradigms to assess fear-related memory in male NMRI mice. Our results showed that the pre-training intraperitoneal administration of ACPA (0.5mg/kg) or (0.1 and 0.5mg/kg) decreased the percentage of freezing time in the contextual and tone fear conditioning, respectively. This indicated an impaired context- or tone-dependent fear memory acquisition. Moreover, the pre-training intra-BLA microinjection of GABA-A receptor agonist, muscimol, at 0.05 and 0.5μg/mouse impaired context-dependent fear memory, while the same doses of GABA-A antagonist, bicuculline, impaired tone-dependent fear memory. However, a subthreshold dose of muscimol or bicuculline increased the effect of ACPA at 0.1 and 0.5 or 0.05mg/kg on context- or tone-dependent fear memory, respectively. In addition, bicuculline at the lower dose increased the ACPA response on locomotor activity compared to its respective group. Such findings highlighted an interaction between BLA GABAergic and cannabinoidergic systems during the acquisition phase of conditioned fear memories.
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, Islamic Azad University, Northern Branch, Tehran, Iran.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Roghani
authors.affiliation: Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran.
authors.forename: Mohaddeseh
authors.initials: M
authors.lastname: Ebrahimi-Ghiri
authors.affiliation: 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; Institute for Cognitive Science Studies (ICSS), 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: D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D063388:Endocannabinoids / Q000494:pharmacology; D005239:Fear / Q000187:drug effects*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D007858:Learning / Q000187:drug effects; D007859:Learning Disabilities; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism* / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D043884:Receptor, Cannabinoid, CB1; D011963:Receptors, GABA-A; C119324:arachidonylcyclopropylamide; D009118:Muscimol; D001640:Bicuculline
keywords: ACPA; Bicuculline; Conditioned fear memory; Mice; Muscimol