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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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Title: The MAGL Inhibitor, JZL184, Attenuates LiCl-Induced Vomiting in the Suncus murinus and 2AG Attenuates LiCl-Induced Nausea-Like Behavior in Rats
Author: Sticht, Martin
Department: Department of Psychology
Program: Psychology
Advisor: Parker, Linda
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.
URI: http://hdl.handle.net/10214/2968
Date: 2011-08
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Citation: Sticht, Long, Rock, Limebeer, Mechoulam, Cravatt, Parker


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