title: Modulation of cannabinoid signaling by amygdala α2-adrenergic system in fear conditioning.
abstract: The noradrenergic system plays a critical role in the modulation of emotional state, primarily related to anxiety, arousal, and stress. Growing evidence suggests that the endocannabinoid system mediates stress responses and emotional homeostasis, in part, by targeting noradrenergic circuits. In addition, there is an interaction between the cannabinoid and noradrenergic system that has significant functional and behavioral implications. Considering the importance of these systems in forming memories for fearful events, we have investigated the involvement of basolateral amygdala (BLA) α2-adrenoceptors on ACPA (as selective cannabinoid CB1 agonist)-induced inhibition of the acquisition of contextual and auditory conditioned fear. A contextual and auditory fear conditioning apparatus for assess fear memory in adult male NMRI mice was used. Pre-training, intraperitoneal administration of ACPA decreased the percentage freezing time in contextual (at doses of 0.05 and 0.1mg/kg) and auditory (at dose of 0.1 mg/kg) in the fear conditioning task, indicating memory acquisition deficit. The same result was observed with intra-BLA microinjection of clonidine (0.001-0.5 μg/mouse, for both memories), as α2-adrenoceptor agonist and yohimbine (at doses of 0.005 and 0.05 for contextual and at dose of 0.05 μg/mouse for auditory fear memory), as α2-adrenoceptor antagonist. In addition, intra-BLA microinjection of clonidine (0.0005 μg/mouse) did not alter ACPA response in both conditions, while the same dose of yohimbine potentiated ACPA response at the lower dose on contextual fear memory. It is concluded that BLA α2-adrenergic receptors may be involved in context- but not tone-dependent fear memory impairment induced by activation of CB1 receptors.
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: Majid
authors.initials: M
authors.lastname: Zamanparvar
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: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000378:metabolism*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D001095:Arachidonic Acids; C578453:CNR1 protein, mouse; D063386:Cannabinoid Receptor Agonists; D043884:Receptor, Cannabinoid, CB1; D018341:Receptors, Adrenergic, alpha-2; C119324:arachidonylcyclopropylamide; D015016:Yohimbine; D003000:Clonidine
keywords: ACPA; Clonidine; Fear memory conditioning; Mice; Yohimbine