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.