The role of D-2 and D-3 dopamine receptors in the mediation of emesis in Cryptotis parva (the least shrew)

This study introduces Cryptotis parva (the least shrew) as a new dopaminerg ic animal model of emesis. The potential emetogenic effects of a nonselecti ve dopamine agonist [apomorphine], two D-1 agonists [SKF-38393 and SKF-8295 8], a D-2 preferring agonist [quinpirole], and two D-3-preferring agonists [7-(OH) DPAT and PD 128, 907] were investigated. Intraperitoneal administra tion of D-1 agonists failed to induce emesis. However, other agonists cause d a dose-dependent increase in the percentage of animals vomiting as well a s potentiating the mean frequency of emesis with the following ED50 potency order: 7-(OH) DPAT < apomorphine < quinpirole < PD 128, 907. For antagonis t studies a 2 mg/kg dose of these agonists were used to induce emesis. Thus , the inhibitory dose-response effects of a D-2-preferring [sulpride], a D- 3-preferring [U 99194A] and combination of varying doses of these antagonis ts [sulpride + U 99194A] were evaluated on the ability of the cited agonist s to produce vomiting. Sulpride decreased the number of shrews vomiting and the mean vomiting frequency produced by the cited agonists in a dose-depen dent fashion with the following ID50 order [apomorphine < PD 128, 907 < 7-( OH) DPAT < quinpirole]. By itself, U 99194A failed to significantly alter t he 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 9 9194A attenuated the potent antiemetic effect of sulpride on the apomorphin e-induced emesis. The results suggest that the tested agonists primarily ac tivate dopamine D-2 receptors to induce emesis in the least shrew whereas a ctivation of D-3 sites potentiate the vomiting action of D-2 dopamine recep tors.