Cannabinoid-induced reduction in antral pacemaker frequency: a telemetric study in the ferret.
BACKGROUND
The gastric myoelectric activity (GMA) is the electrical pacesetter potential, which drives gastric motility. Cannabinoids have broad-spectrum antiemetic and antinauseant activity. Paradoxically, they inhibit intestinal peristalsis and reduce gastric motility but their effect on GMA remains unknown.


METHODS
Ferrets were surgically implanted with radiotelemetry transmitters to record GMA, body temperature and heart rate. The effect of WIN 55,212-2 (1 mg kg(-1), i.p.), an agonist at the cannabinoid type 1 and 2 receptors was examined in conscious, unrestrained ferrets. WIN 55,212-2 was also compared to the anandamide upregulator URB 597 (5 mg kg(-1), i.p.) for a potential to modulate the emetic response and behavioral changes induced by apomorphine (0.25 mg kg(-1), s.c.).


RESULTS
WIN 55,212-2 decreased GMA frequency (8.1 ± 0.4 cpm, compared to 9.6 ± 0.1 cpm in vehicle-treated animals, n = 6, P < 0.01). Apomorphine induced 9.0 ± 1.6 emetic episodes, WIN 55,212-2 inhibited the emetic response (3.3 ± 1.0 episodes, n = 6, P < 0.05) but URB 597 had no effect (9.0 ± 1.5 episodes). Apomorphine-induced hyperactivity in vehicle-treated animals (6.5 ± 3.6-16.6 ± 4.9 active behavior counts, n = 6, P < 0.01), which was reduced by WIN 55,212-2 (5.0 ± 1.5 counts, n = 6, P < 0.05).


CONCLUSIONS
WIN 55,212-2 demonstrated clear antiemetic efficacy, which extends the broad-spectrum antiemetic efficacy of cannabinoids to dopamine receptor agonists in the ferret. Our results, however, suggest a more limited spectrum of action for URB 597. WIN 55,212-2 decreased the frequency of the antral electrical pacemaker, which reveals new insights into the mechanism regulating the decrease in motility induced by cannabinoids.
Percie du Sert
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Division of Basic Medical Sciences, St George's University of London, London, UK. npercied@sgul.ac.uk
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W-S V
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Rudd
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JA
Andrews
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D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D001058:Apomorphine; D001549:Benzamides / Q000494:pharmacology; D001683:Biological Clocks / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D002186:Cannabinoids / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology; D004639:Emetics; D005260:Female; D005289:Ferrets / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D016065:Myoelectric Complex, Migrating / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists; D013686:Telemetry; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001058:Apomorphine; D001549:Benzamides; D002186:Cannabinoids; D002219:Carbamates; D004639:Emetics; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester