title: Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats.
abstract: The present study investigated the central effects of the eCB uptake/metabolism inhibitor AM404 and the phytocannabinoid cannabidiol (CBD) on the extinction of contextual fear memories in rats. Rats were conditioned and 24 h later subjected to three consecutive 9-min non-reinforced exposures to the conditioning context (extinction sessions, 24 h intervals). AM404 or CBD was injected i.c.v. 5 min before each extinction session and a 3-min drug-free test of contextual memory was performed 24 h after the last extinction session. AM404 (1.0 microg/microl, i.c.v.) and CBD (2.0 microg/microl, i.c.v.) facilitated extinction of contextual fear memory, with persistent effects. These responses were antagonized by the CB1-selective antagonist SR141716A (0.2 mg/kg, i.p.), but not by the TRPV1-selective antagonist capsazepine (5.0 microg/microl, i.c.v.). The effect of the anxiolytic drug Diazepam (DZP) on the extinction of contextual fear memory was also investigated. In contrast with the CBD and AM404 results, DZP induced a general reduction in the expression of conditioned freezing. Both AM404 and CBD induced anti-anxiogenic effect in the fear-potentiated plus-maze test, whereas DZP was anxiolytic in conditioned and unconditioned rats. In conclusion, CBD, a non-psychoactive phytocannabinoid could be an interesting pharmacological approach to reduce the anxiogenic effects of stress and promote the extinction of fear memories.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis-SC, Brazil.
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Bitencourt
authors.forename: Fabrício A
authors.initials: FA
authors.lastname: Pamplona
authors.forename: Reinaldo N
authors.initials: RN
authors.lastname: Takahashi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002185:Cannabidiol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077285:Rimonabant; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors
chemical_list: D014151:Anti-Anxiety Agents; D001095:Arachidonic Acids; D010880:Piperidines; D011720:Pyrazoles; D050916:TRPV Cation Channels; D002185:Cannabidiol; C071423:capsazepine; D000077285:Rimonabant; D002211:Capsaicin; C107594:N-(4-hydroxyphenyl)arachidonylamide