title: Attenuation of anticipatory nausea in a rat model of contextually elicited conditioned gaping by enhancement of the endocannabinoid system.
abstract: BACKGROUND
  Enhancement of the endocannabinoid (EC) system may reduce anticipatory nausea (AN).
  
  
  OBJECTIVE
  The experiments evaluated the potential of the dual fatty acid amide hydrolase (FAAH)/monoacylglycerol lipase (MAGL) inhibitor, JZL195, on its own and combined with anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) to reduce contextually elicited gaping, a measure of AN in rats.
  
  
  METHODS
  Following four context lithium chloride (LiCl) pairings, rats were injected with vehicle (VEH) or JZL195 (10 mg kg(-1), intraperitoneally) 105 min before an injection of VEH, 2-AG (1.25 mg kg(-1)), or AEA (5.0 mg kg(-1)). Fifteen minutes later, all rats were placed in the LiCl-paired context for 5 min and in a different context for a 15-min locomotor test. Whole brains were extracted for EC analysis. The potential of the CB1 antagonist, SR141716, to reverse the suppression of AN by both JZL195 and AEA and of the CB2 antagonist, AM630, to reverse the suppression of AN by JZL195 was then evaluated.
  
  
  RESULTS
  JZL195 suppressed gaping and elevated AEA, palmitoylethanolamine, and oleoylethanolamide. As the suppression of gaping was reversed by SR141716, but not by AM630, the effect was CB1 mediated. The suppressive effect of JZL195 on gaping, as well as elevation of AEA and 2-AG, was amplified by pretreatment with either AEA or 2-AG. On its own, AEA, but not 2-AG, also suppressed gaping-an effect that was also prevented by CB1 antagonism.
  
  
  CONCLUSIONS
  JZL195 reduces AN primarily by acting as a FAAH inhibitor, but MAGL inhibition is also indicated.
authors.affiliation: Department of Psychology and Neuroscience Graduate Program, University of Guelph, Guelph, ON, N1H 2W1, Canada.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Limebeer
authors.forename: Rehab A
authors.initials: RA
authors.lastname: Abdullah
authors.forename: Erin M
authors.initials: EM
authors.lastname: Rock
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Imhof
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Aron H
authors.initials: AH
authors.lastname: Lichtman
authors.forename: Linda A
authors.initials: LA
authors.lastname: Parker
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D059031:Anticipation, Psychological / Q000187:drug effects / Q000502:physiology*; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D063388:Endocannabinoids / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005989:Glycerides / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D018021:Lithium Chloride; D008297:Male; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009325:Nausea / Q000188:drug therapy / Q000503:physiopathology*; D009829:Oleic Acids / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D063387:Cannabinoid Receptor Antagonists; D002219:Carbamates; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; D007211:Indoles; D018021:Lithium Chloride; D008994:Monoacylglycerol Lipases; D009829:Oleic Acids; D010879:Piperazines; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000077285:Rimonabant; D000099252:Fatty Acid Amide Hydrolases; C000592052:JZL195; C488250:oleoylethanolamide; C094503:glyceryl 2-arachidonate; C094023:iodopravadoline; C078814:anandamide
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