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188 L.A. Parker et al.
Cats and dogs
Although the two studies that evaluated the potential of nabilone [(0.1 mg/kg,
administered intravenously (iv)] to antagonize cisplatin-induced emesis [67]
and apomorphine-induced emesis [68] in dogs failed to find an anti-emetic
effect of the cannabinoid, studies with cats have shown more promising
results. McCarthy and Borison [30] reported that the synthetic cannabinoids
methyllevonantradol (0.003–0.02 mg/kg, iv) and nabilone (0.025–0.1 mg/kg,
iv) protected cats against cisplatin-induced vomiting and reduced the number
of vomiting episodes among cats not protected in a dose-dependent manner.
Pigeons
An early study [65] with pigeons demonstrated that the non-psychotropic synthetic
cannabinoid, HU-211, was more effective than ∆ 9 -THC in suppressing
cisplatin-induced vomiting. The anti-emetic effect of HU-211 was U-shaped
over a narrow dose range, with maximal efficacy at 2.5 and 3 mg/kg, administered
subcutaneously (sc). More recently, the potent psychoactive cannabinoid,
HU-210 (0.0125–0.05 mg/kg, sc) has also been reported to suppress cisplatin-induced
vomiting in the pigeon [66].
Ferrets
One of the most widely used animal models of emesis is the ferret. In this
model, morphine-induced emesis [33] was suppressed by the synthetic
cannabinoid agonist WIN-55,212-2 (0.03–0.13 mg/kg, sc) and this effect was
reversed by the selective CB 1 receptor antagonist, AM-251. Van Sickle et al.
[34] report that the emesis produced by morphine-6-glucuronide (M6G; sc) in
ferrets was also inhibited by ∆ 9 -THC [1 mg/kg, administered intraperitoneally
(ip)], WIN-55,212-2 (1 mg/kg, ip) and methanandamide (3 mg/kg, ip), and that
this anti-emetic effect was also reversed by AM-251 (5 mg/kg, ip). Although
AM-251 did not produce emetic episodes on its own, it did potentiate the emetogenic
effects of M6G [34]. More recently, ∆ 9 -THC (0.05–1 mg/kg, ip)
dose-dependently inhibited the emetic actions of cisplatin [35]. Furthermore,
∆ 9 -THC applied to the surface of the brain stem also inhibited emesis induced
by intragastric hypertonic saline [35].
Shrews
Insectivores, such as the shrew, are the closest extant relatives to primates as
well as the oldest group of eutherians. Insectivores have sensitive emetic
reflexes. Shrews are smaller than carnivores (such as cats, dogs and ferrets)