title: FAAH inhibitor OL-135 disrupts contextual, but not auditory, fear conditioning in rats.
abstract: Anxiety disorders are among the most prevalent psychological disorders, have significant negative impacts on quality of life and the healthcare system, and yet effective treatments remain elusive. Manipulating the endocannabinoid system has demonstrated potential for treating anxiety, although the side effects of direct manipulations of cannabinoid receptors keeps them from widespread clinical use. Disrupting the degradation enzyme fatty acid amide hydrolase (FAAH) enhances endogenous signaling and may produce similar efficacy without the side effects. The current experiments examine the effects of low (5.6mg/kg) or moderate (10.0mg/kg) doses of OL-135, a FAAH inhibitor, on the acquisition and consolidation of classical fear conditioning, a common model of trauma-induced anxiety. The acquisition of contextual, but not auditory, fear conditioning was disrupted by both doses of OL-135. Shock reactivity was not affected. Due to the additional neural circuitry required for contextual, but not auditory, fear conditioning, these data suggest that endocannabinoid signaling outside the amygdala may be critical for a subset of fearful memories.
authors.affiliation: Department of Psychology, United States; Center for Excellence in the Neurosciences, University of New England, United States. Electronic address: mburman@une.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Burman
authors.affiliation: Department of Psychology, United States; Center for Excellence in the Neurosciences, University of New England, United States.
authors.forename: Kerribeth
authors.initials: K
authors.lastname: Szolusha
authors.affiliation: Center for Excellence in the Neurosciences, University of New England, United States.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bind
authors.affiliation: Center for Excellence in the Neurosciences, University of New England, United States.
authors.forename: Kristen
authors.initials: K
authors.lastname: Kerney
authors.affiliation: Department of Chemistry, The Scripps Research Institute, United States.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Boger
authors.affiliation: Department of Biomedical Sciences, United States; Center for Excellence in the Neurosciences, University of New England, United States.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Bilsky
mesh_terms: D000161:Acoustic Stimulation; D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects*; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D011725:Pyridines; D000099252:Fatty Acid Amide Hydrolases; C495479:1-oxo-1-(5-(2-pyridyl)-2-yl)-7-phenylheptane