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Cannabinoid-induced reduction in antral pacemaker frequency: a telemetric study in the ferret
N Percie du Sert1, W-S V Ho, J A Rudd
1Division of Basic Medical Sciences, St George's University of London, London, UK. npercied@sgul.ac.uk
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.).
Key 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 & Inferences:
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.
