The MAGL Inhibitor, JZL184, Attenuates LiCl-Induced Vomiting in the Suncus murinus and 2AG Attenuates LiCl-Induced Nausea-Like Behavior in Rats

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The MAGL Inhibitor, JZL184, Attenuates LiCl-Induced Vomiting in the Suncus murinus and 2AG Attenuates LiCl-Induced Nausea-Like Behavior in Rats

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dc.contributor.advisor Parker, Linda
dc.contributor.author Sticht, Martin
dc.date 2009-08-17
dc.date.accessioned 2011-09-09T18:36:59Z
dc.date.available 2011-09-09T18:36:59Z
dc.date.issued 2011-04-06
dc.identifier.citation Sticht, Long, Rock, Limebeer, Mechoulam, Cravatt, Parker en_US
dc.identifier.uri http://hdl.handle.net/10214/2968
dc.description.abstract The role of 2-arachidonoylglycerol (2-AG) in nausea and vomiting was evaluated using a shrew (Suncus murinus) model of emesis and nausea-like behavior in rats, conditioned gaping. Shrews received JZL184, a selective MAGL inhibitor, prior to treatment with emetogenic lithium chloride (LiCl). The potential of exogenously administered 2-AG and arachidonic acid (AA) to regulate conditioned gaping was assessed in rats. The role of cannabinoid receptors and cyclooxygenase (COX) inhibition in suppression of vomiting and conditioned gaping was also evaluated. JZL184 dose-dependently suppressed vomiting in shrews, and was shown to inhibit MAGL in shrew brain tissue. The anti-emetic effects of JZL184 were prevented by the CB1 antagonist, AM251. Exogenous 2-AG suppressed LiCl-induced conditioned gaping, but was not prevented by AM251 or the CB2 antagonist, AM630. Instead, the COX inhibitor, indomethacin, prevented the suppressive effects of 2-AG, as well as AA. These results suggest that manipulations that elevate 2-AG may have anti-emetic/anti-nausea potential. en_US
dc.description.sponsorship This research was supported by research grants from the Natural Sciences and Engineering Research Council of Canada (NSERC 92057) to Linda Parker, the Israel Science Foundation (DA009789) to Raphael Mechoulam, and the National Institutes of Health (DA009789, DA017259) to Benjamin Cravatt. en_US
dc.language.iso en en_US
dc.publisher British Journal of Pharmacology en_US
dc.subject MAGL en_US
dc.subject 2AG en_US
dc.subject CB1 Receptor en_US
dc.subject cyclooxygenase en_US
dc.subject nausea en_US
dc.subject vomiting en_US
dc.subject learning en_US
dc.subject gaping en_US
dc.subject taste reactivity en_US
dc.title The MAGL Inhibitor, JZL184, Attenuates LiCl-Induced Vomiting in the Suncus murinus and 2AG Attenuates LiCl-Induced Nausea-Like Behavior in Rats en_US
dc.type Article en_US
dc.degree.programme Psychology en_US
dc.degree.name Master of Science en_US
dc.degree.department Department of Psychology en_US


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