title: Differential effects of CB1 receptor agonism in behavioural tests of unconditioned and conditioned fear in adult male rats.
abstract: We investigated the effects of the highly selective CB1 receptor agonist ACEA and the CB1 receptor antagonist/inverse agonist AM251 on two behavioural tests of unconditioned fear, the elevated plus maze (EPM) and open field test (OFT), as well as on the recall and extinction of a conditioned auditory fear. Both ACEA and AM251 increased anxiety-like behaviour in the EPM and OFT. There was no effect of either drug on recall of the conditioned fear, and ACEA enhanced and AM251 impaired fear extinction. Further, though both the low (0.1 mg/kg) and high (0.5 mg/kg) dose of ACEA facilitated fear extinction, the low dose attenuated, and the high dose potentiated, fear induced corticosterone release suggesting independent effects of the drug on fear and stress responses. Although the extent to which cannabinoids are anxiogenic or anxiolytic has been proposed to be dose-dependent, these results indicate that the same dose has differential effects across tasks, likely based in differences in sensitivities of CB1 receptors to the agonist in the neural regions subserving unconditioned and conditioned fear.
authors.affiliation: Department of Biological Sciences, Brock University, 500 Glenridge Ave., St. Catharines, ON L2S 3A1, Canada. Electronic address: js09vp@brocku.ca.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Simone
authors.affiliation: Department of Psychology, Brock University, 500 Glenridge Ave., St. Catharines, ON L2S 3A1, Canada. Electronic address: mg06mc@brocku.ca.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Green
authors.affiliation: Department of Psychology, Brock University, 500 Glenridge Ave., St. Catharines, ON L2S 3A1, Canada. Electronic address: th12iw@brocku.ca.
authors.forename: Travis E
authors.initials: TE
authors.lastname: Hodges
authors.affiliation: Department of Biological Sciences, Brock University, 500 Glenridge Ave., St. Catharines, ON L2S 3A1, Canada; Department of Psychology, Brock University, 500 Glenridge Ave., St. Catharines, ON L2S 3A1, Canada. Electronic address: cmccormick@brocku.ca.
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: McCormick
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology*; D001095:Arachidonic Acids / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C119325:arachidonyl-2-chloroethylamide; C103505:AM 251; D003345:Corticosterone
keywords: CB1 receptor agonism; CB1 receptor antagonism; Conditioned fear; Physiological stress; Unconditioned fear