Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret

Citation
Md. Van Sickle et al., Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret, GASTROENTY, 121(4), 2001, pp. 767-774
Citations number
36
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
GASTROENTEROLOGY
ISSN journal
00165085 → ACNP
Volume
121
Issue
4
Year of publication
2001
Pages
767 - 774
Database
ISI
SICI code
0016-5085(200110)121:4<767:CIETCR>2.0.ZU;2-C
Abstract
Background & Aims: Marijuana and other cannabinoids are effective anti-emet ics. Despite ongoing controversy over their usage, the receptor distributio n and the site of the anti-emetic action of these compounds are not known. Our aim was to investigate whether the cannabinoid I receptor (CB1r) and en docannabinoids play a role in the anti-emetic action of cannabinoids. Metho ds: Ferrets were given an emetic stimulus and the number of episodes of ret ching and vomiting were observed after administration of CB1r agonists and a CB1r antagonist. CB1r and fatty acid amide hydrolase (FAAH), which degrad es endocannabinoids, were localized by immunohistochemistry. Results: CB1r and FAAH were localized in the dorsal vagal complex, consisting of the area postrema, nucleus of the solitary tract, and the dorsal motor nucleus of t he vagus in the brainstem. CB1r was found in the myenteric plexus of the st omach and duodenum. Activation of CB1r by the agonists (delta)(9)-tetrahydr ocannabinol, WIN 55,212-2, and methanandamide inhibited emesis and their ac tion was reversed by a selective CB1r antagonist, which alone had no effect , but potentiated vomiting in response to an emetic stimulus. Conclusions: CB1r mediates the antiemetic action of cannabinoids in the dorsal vagal com plex. Endocannabinoids are a novel neuroregulatory system involved in the c ontrol of emesis.