title: Interplay between serotonin and cannabinoid function in the amygdala in fear conditioning.
abstract: The possible interactions between the cannabinoid and serotonin systems in the regions of the brain involved in emotional learning and memory formation have been studied by some researchers. In view of the key role of the amygdala in the acquisition and expression of fear memory, we investigated the involvement of basolateral amygdala (BLA) serotonin 5-HT4 receptors in arachidonylcyclopropylamide (ACPA; selective CB1 cannabinoid receptor agonist)-induced fear memory consolidation impairment. In our study, a context and tone fear conditioning apparatus was used for testing fear conditioning in adult male NMRI mice. The results showed that intraperitoneal administration of ACPA 0.5 or 0.05, 0.1 and 0.5mg/kg immediately after training decreased the percentage of freezing time in context or tone fear conditioning respectively, suggesting a context- or tone-dependent fear memory consolidation impairment. Post-training intra-BLA microinjections of RS67333, as 5-HT4 serotonin receptor agonist, at doses of 0.025 and 0.05 µg/mouse also impaired context or tone memory consolidation, while RS23597, as 5-HT4 serotonin receptor antagonist, did not produce a marked difference in both fear memories as compared with the control group. Moreover, a subthreshold dose of RS67333 did not alter ACPA response in both fear conditionings. Interestingly, a subthreshold dose of RS23597 potentiated or reversed ACPA response at the dose of 0.01 or 0.05 respectively. It is concluded that BLA serotonin 5-HT4 receptors are involved in tone-dependent fear memory consolidation impairment induced by CB1 activation using ACPA, suggesting a modulatory role for serotonin 5-HT4 receptor.
authors.affiliation: Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
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: Kamelia
authors.initials: K
authors.lastname: Davoudi
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: Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, 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; 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: D000161:Acoustic Stimulation; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000633:toxicity; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D002186:Cannabinoids / Q000378:metabolism*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced; D051379:Mice; D008845:Microinjections; D010880:Piperidines / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology
chemical_list: D000814:Aniline Compounds; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D010880:Piperidines; D018490:Serotonin Agents; C119324:arachidonylcyclopropylamide; C107826:RS 67333; D012701:Serotonin
keywords: ACPA; Fear memory conditioning; Mice; RS23597; RS67333