Rapid CommunicationsCannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret☆,☆☆
Section snippets
Behavioral experiments
Adult ferrets (900–1500g, Mustela putoris furo, Marshall Research Labs, NY) were used for all studies. These experiments were conducted in accordance with the guidelines established by the Canadian Council on Animal Care and were approved by the University of Calgary Health Sciences Animal Care Committee. Animals were fasted overnight before experimentation.
Three series of studies were conducted. In the first series, animals received a cannabinoid agonist (intraperitoneally [IP]) or its vehicle
Behavioral experiments
The naturally occurring CB1r agonist, THC (1 mg/kg) virtually abolished the emetic effect of M6G in the ferret (0.05 mg/kg, P < 0.001, Figure 1A).
Discussion
The anti-emetic effect of CB1r agonists and their reversal by a selective CB1r antagonist support the hypothesis that the CB1r mediates the anti-emetic action of cannabinoids. A similar result has recently been shown using WIN 55,212-2 against morphine-induced emesis in the ferret.19 If an endogenous system of cannabinoids exists to modulate the emetic response, receptor antagonism itself might be expected to have an effect on emesis. This was demonstrated by the increase in vomiting and
Acknowledgements
The authors thank Drs. A. Mouihate and Q. J. Pittman for assistance with the Western Immunoblotting. A preliminary account of this work was presented at the Digestive Disease Week, May 2001 (Gastroenterology 2001;120:A197).
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Address requests for reprints to: Keith A. Sharkey, Ph.D., Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive N.W., Calgary, Canada AB T2N 4N1. e-mail: [email protected]; fax: (403) 283-2700.
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Supported by grants from the Canadian Institutes of Health Research (to K.A.S. and J.S.D.) and the National Institutes of Health (DA00286 and DA11322 to K.M., DA09155 to C.J.H.). K.A.S. is an Alberta Heritage Foundation for Medical Research Medical Scientist.