Abstract
Considerable evidence implicates the endocannabinoid system as a neuromodulator of nausea and vomiting. The action of anandamide (AEA) can be prolonged by inhibiting its degradation, through the use of URB597 (URB), a Fatty Acid Amide Hydrolase (FAAH) enzyme inhibitor. Here we present evidence that the FAAH inhibitor, URB, interferes with cisplatin- and nicotine-induced vomiting in the Suncus murinus. In Experiment 1, shrews were injected with URB (0.9 mg/kg) or vehicle 120 min prior to the behavioral testing. They received a second injection of AEA (5 mg/kg) or vehicle 15 min prior to being injected with cisplatin (20 mg/kg) or saline and the number of vomiting episodes were counted for 60 min. In Experiment 2, shrews were injected with vehicle or URB (0.9 mg/kg) 120 min prior to receiving an injection of nicotine (5 mg/kg) or saline and the number of vomiting episodes were counted for 15 min. Experiment 3 evaluated the potential of the CB 1 antagonist, SR141716, to reverse the effect of URB on nicotine-induced vomiting. URB attenuated vomiting produced by cisplatin and nicotine and the combination of URB + AEA suppressed vomiting produced by cisplatin. The effect of URB on nicotine-induced vomiting was reversed by SR141716. These data suggest that the EC system plays a tonic role in the regulation of toxin-induced vomiting.
Highlights
Considerable evidence implicates the endocannabinoid system as a neuromodulator of nausea and vomiting [see 1, 2]
arachidonylethanolamide or anandamide (AEA) alone did not significantly reduce vomiting, when its action was presumably prolonged by pretreatment with the Fatty Acid Amide Hydrolase (FAAH) inhibitor, cisplatin-induced vomiting was suppressed in the Suncus murinus
Even when AEA was not exogenously administered, URB suppressed cisplatin-induced vomiting, suggesting that the action of the endocannabinoid was enhanced by pretreatment with the FAAH inhibitor
Summary
Considerable evidence implicates the endocannabinoid system as a neuromodulator of nausea and vomiting [see 1, 2]. The anti-emetic properties of cannabinoid drugs extend beyond humans [3] to include other emetic species such as pigeons [4], ferrets [5, 6], cats [7], least shrews, Cryptostis parva [e.g. 8] and the house musk shrew Suncus murinus [9, 10]. SR141716 produces vomiting on its own at higher doses [8]. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain
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