Considerable evidence supports anandamide (AEA) as an important mediator in the regulation of nausea and vomiting. The present study investigates the effect of inhibiting a protein reported to mediate AEA transport, FLAT (FAAH-1-like AEA transporter), on nausea and vomiting and the neural correlates of AEA regulated nausea in the visceral insular cortex (VIC). The systemic administration of the AEA transport inhibitor ARN272 was evaluated in LiCl-induced conditioned gaping in rats, and vomiting in shrews. The effect of intra-cranial administration of ARN272 into the VIC was also investigated using LiCl-induced conditioned gaping in rats. Systemic administration of ARN272 dose-dependently suppressed LiCl-induced conditioned gaping in rats, and was reversed by CB1 receptor antagonism with SR141716. Systemic administration of ARN272 also attenuated vomiting in shrews. Delivery of ARN272 into the VIC produced no effect on LiCl-induced conditioned gaping in rats. These results suggest that preventing the cellular reuptake of AEA through transport inhibition tonically activates CB1 receptors to regulate toxin-induced nausea, but that this is not AEA regulated within the VIC. / This research was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC-92057) to LAP.