The Role of D2 and D3 Dopamine Receptors in the Mediation of Emesis in Cryptotis Parva (the Least Shrew)

This study introduces Cryptotis parva (the least shrew) as a new dopaminergic animal model of emesis. The potential emetogenic effects of a nonselective dopamine agonist [apomorphine], two D1 agonists [SKF-38393 and SKF-82958], a D2 preferring agonist [quinpirole], and two D3-preferring agonists [7-(OH) DPAT and PD 128, 907] were investigated. Intraperitoneal administration of D1 agonists failed to induce emesis. However, other agonists caused a dose-dependent increase in the percentage of animals vomiting as well as potentiating the mean frequency of emesis with the following ED50, potency order: 7-(OH) DPAT < apomorphine < quinpirole < PD 128, 907. For antagonist studies a 2 mg/kg dose of these agonists were used to induce emesis. Thus, the inhibitory dose-response effects of a D2-preferring [sulpride], a D3-preferring [U 99194A] and combination of varying doses of these antagonists [sulpride + U 99194A] were evaluated on the ability of the cited agonists to produce vomiting. Sulpride decreased the number of shrews vomiting and the mean vomiting frequency produced by the cited agonists in a dose-dependent fashion with the following ID50 order [apomorphine < PD 128, 907 < 7-(OH) DPAT < quinpirole]. By itself, U 99194A failed to significantly alter the emesis produced by any of the cited agonists, however, it potentiated (3-8 times) the antiemetic effects of sulpride both in reducing the number of shrews vomiting as well as decreasing the mean vomiting frequency with the following ID50 order: PD 128, 907 < 7-(OH) DPAT < quinpirole. However, U 99194A attenuated the potent antiemetic effect of sulpride on the apomorphine-induced emesis. The results suggest that the tested agonists primarily activate dopamine D2 receptors to induce emesis in the least shrew whereas activation of D3 sites potentiate the vomiting action of D2 dopamine receptors.