title: The CB1 receptor antagonist AM251 impairs reconsolidation of pavlovian fear memory in the rat basolateral amygdala.
abstract: We have investigated the requirement for signaling at CB1 receptors in the reconsolidation of a previously consolidated auditory fear memory, by infusing the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the basolateral amygdala (BLA) in conjunction with memory reactivation. AM251 disrupted memory restabilization, but only when administered after reactivation. URB597 produced a small, transient enhancement of memory restabilization when administered after reactivation. The amnestic effect of AM251 was rescued by coadministration of the GABAA receptor antagonist bicuculline at reactivation, indicating that the disruption of reconsolidation was mediated by altered GABAergic transmission in the BLA. These data show that the endocannabinoid system in the BLA is an important modulator of fear memory reconsolidation and that its effects on memory are mediated by an interaction with the GABAergic system. Thus, targeting the endocannabinoid system may have therapeutic potential to reduce the impact of maladaptive memories in neuropsychiatric disorders such as posttraumatic stress disorder.
authors.affiliation: 1] Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge, UK [2] Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ratano
authors.affiliation: Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge, UK.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Everitt
authors.affiliation: Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge, UK.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Milton
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology; D066272:Basolateral Nuclear Complex / Q000187:drug effects* / Q000502:physiology; D001549:Benzamides / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology; D003214:Conditioning, Classical; D004597:Electroshock; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001549:Benzamides; D001640:Bicuculline; D063387:Cannabinoid Receptor Antagonists; D002219:Carbamates; D004791:Enzyme Inhibitors; D058787:GABA-A Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D011963:Receptors, GABA-A; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C103505:AM 251