Involvement of dopamine D-3 receptors in the area postrema in R(+)-7-OH-DPAT-induced emesis in the ferret

We investigated the possible involvement of dopamine D-3 receptors in R(+)-7-hydroxy-2-(N, N-di-n-propylamino)tetraline (R(+)-7-OH-DPAT)-induced emesis in the ferret. The R(+)enantiomer of 7-OH-DPAT (0.03-1 mg/kg, s.c.) caused emesis in a dose-dependent manner, whereas the S(-)enantiomer, even at 1 mg/kg s.c. failed to induce emesis. Quinpirole (0.1-1.0 mg/kg) and apomorphine (0.3 mg/kg, s.c. only) also elicited an emetic response. S(-)-Eticlopride, which has a high affinity for the dopamine D-3 receptor, antagonized R(+)-7-OH-DPAT (0.3 mg/kg, s.c.)-induced emesis (ID50 1.4 mu g/kg, s.c.). R(+)-7-OH-DPAT (0.1-1.0 mu g) administered into the 4th cerebral ventricle dose dependently induced emesis within 1 min of dosing in ferrets. Intracerebroventricularly administered S(-)-eticlopride (0.01-1 mu g) also inhibited the emesis induced by s.c. administration of R(+)-7-OH-DPAT. The emetic effect of R(+)-7-OH-DPAT was unaffected by abdominal vagotomy but was markedly reduced by ablation of the area postrema. These results suggest that dopamine D-3 receptors in the area postrema play an important role in R(+)-7-OH-DPAT-induced emesis in the ferret.