title: Elevation of 2-AG by monoacylglycerol lipase inhibition in the visceral insular cortex interferes with anticipatory nausea in a rat model.
abstract: Anticipatory nausea (AN) is a conditioned nausea reaction experienced by chemotherapy patients upon returning to the clinic. Currently, there are no specific treatments for this phenomenon, with the classic antiemetic treatments (e.g., ondansetron) providing no relief. The rat model of AN, contextually elicited conditioned gaping reactions in rats, provides a tool for assessing potential treatments for this difficult to treat disorder. Systemically administered drugs which elevate the endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), by interfering with their respective degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) interfere with AN in the rat model. We have shown that MAGL inhibition within the visceral insular cortex (VIC) interferes with acute nausea in the gaping model (Sticht et al., 2015). Here we report that bilateral infusion of the MAGL inhibitor, MJN110 (but neither the FAAH inhibitor, PF3845, nor ondansetron) into the VIC suppressed contextually elicited conditioned gaping, and this effect was reversed by coadministration of the CB1 antagonist, AM251. These findings suggest that 2-AG within the VIC plays a critical role in the regulation of both acute nausea and AN. Because there are currently no specific therapeutics for chemotherapy patients that develop anticipatory nausea, MAGL inhibition by MJN110 may be a candidate treatment. (PsycINFO Database Record
authors.affiliation: Department of Psychology, University of Guelph.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Limebeer
authors.affiliation: Department of Psychology, University of Guelph.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Rock
authors.affiliation: Department of Psychology, University of Guelph.
authors.forename: Nirushan
authors.initials: N
authors.lastname: Puvanenthirarajah
authors.affiliation: Skaggs Institute for Chemical Biology, Scripps Research Institute.
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Niphakis
authors.affiliation: Skaggs Institute for Chemical Biology, Scripps Research Institute.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Cravatt
authors.affiliation: Department of Psychology, University of Guelph.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Parker
mesh_terms: D000581:Amidohydrolases; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects*; D063388:Endocannabinoids / Q000378:metabolism* / Q000627:therapeutic use; D005989:Glycerides / Q000378:metabolism* / Q000627:therapeutic use; D018021:Lithium Chloride / Q000494:pharmacology; D023421:Models, Animal; D008994:Monoacylglycerol Lipases / Q000187:drug effects* / Q000378:metabolism; D009325:Nausea; D053284:Polyunsaturated Alkamides; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin; D014840:Vomiting, Anticipatory / Q000628:therapy; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D018021:Lithium Chloride; D008994:Monoacylglycerol Lipases; D053284:Polyunsaturated Alkamides; D012701:Serotonin; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate; C078814:anandamide