title: The endogenous cannabinoid anandamide shares discriminative stimulus effects with ∆(9)-tetrahydrocannabinol in fatty acid amide hydrolase knockout mice.
abstract: The endogenous cannabinoid system has been noted for its therapeutic potential, as well as the psychoactivity of cannabinoids such as Δ9-tetrahydrocannabinol (THC). However, less is known about the psychoactivity of anandamide (AEA), an endocannabinoid ligand. Thus, the goals of this study were to establish AEA as a discriminative stimulus in transgenic mice lacking fatty acid amide hydrolase (i.e., FAAH -/- mice unable to rapidly metabolize AEA), evaluate whether THC or oleamide, a fatty acid amide, produced AEA-like responding, and assess for CB(1) mediation of AEA's discriminative stimulus. Mice readily discriminated between 6mg/kg AEA and vehicle in a two-lever drug discrimination task. AEA dose-dependently generalized to itself. THC elicited full AEA-like responding, whereas oleamide failed to substitute. The CB(1) antagonist rimonabant attenuated AEA- and THC-induced AEA-appropriate responding, demonstrating CB(1) mediation of AEA's discriminative stimulus. These findings suggest that, in the absence of FAAH, AEA produces intoxication comparable to THC, and consequently to marijuana.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, PO BOX 980613, Richmond, VA 23298-0613, United States.
authors.forename: D Matthew
authors.initials: DM
authors.lastname: Walentiny
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gamage
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Warner
authors.forename: Thanh K
authors.initials: TK
authors.lastname: Nguyen
authors.forename: Darren B
authors.initials: DB
authors.lastname: Grainger
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Wiley
authors.forename: Robert E
authors.initials: RE
authors.lastname: Vann
mesh_terms: D000581:Amidohydrolases / Q000172:deficiency* / Q000235:genetics*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D013759:Dronabinol / Q000494:pharmacology*; D063388:Endocannabinoids; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D009829:Oleic Acids / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D013759:Dronabinol; D063388:Endocannabinoids; D009829:Oleic Acids; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C029407:oleylamide; C078814:anandamide