title: Just add water: cannabinoid discrimination in a water T-maze with FAAH(-/-) and FAAH(+/+) mice.
abstract: Incomplete overlap in the discriminative stimulus effects of Δ-tetrahydrocannabinol (THC) and the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol has been reported in food-reinforced tasks. The aim of this study was to examine cannabinoid discriminative stimulus effects in a nonappetitive procedure. Adult male mice lacking the gene for AEA's major metabolic enzyme, fatty acid amide hydrolase (FAAH), and FAAH mice were trained to discriminate THC or AEA in a water T-maze, in which the response was swimming to an escape platform on the injection-appropriate side. JZL184, a monoacylglycerol lipase inhibitor, was also tested. FAAH mice showed faster acquisition than FAAH mice. THC and AEA fully substituted, with only minor cross-procedure potency variations. Incomplete substitution of JZL184 was observed in THC-trained FAAH mice in the water-maze task, as contrasted with full substitution in a food-reinforced nose-poke procedure. Stress-induced changes in AEA and/or 2-arachidonoylglycerol concentrations in the brain may have mediated this attenuation. JZL184 also partially substituted in AEA-trained FAAH mice in the water maze, suggesting incomplete overlap in the stimulus effects of AEA and JZL184. Through the use of a novel water-maze procedure, the present study supports the work of previous behavioral pharmacologists in showing the robustness of the discrimination paradigm.
authors.affiliation: aRTI International, Research Triangle Park, North CarolinabThe Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CaliforniacDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Wiley
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Lefever
authors.forename: Nikita S
authors.initials: NS
authors.lastname: Pulley
authors.forename: Julie A
authors.initials: JA
authors.lastname: Marusich
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Cravatt
authors.forename: Aron H
authors.initials: AH
authors.lastname: Lichtman
mesh_terms: D000581:Amidohydrolases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D004192:Discrimination, Psychological / Q000187:drug effects; D013759:Dronabinol / Q000494:pharmacology*; D063388:Endocannabinoids / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D014867:Water; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D052117:Benzodioxoles; D013759:Dronabinol; D063388:Endocannabinoids; D005989:Glycerides; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D014867:Water; D000099252:Fatty Acid Amide Hydrolases; C534333:JZL 184; C094503:glyceryl 2-arachidonate; C078814:anandamide