Involvement of dopamine D3 receptors in the area postrema in R(+)-7-OH-DPAT-induced emesis in the ferret.
We investigated the possible involvement of dopamine D3 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 D3 receptor, antagonized R(+)-7-OH-DPAT (0.3 mg/kg, s.c.)-induced emesis (ID50 1.4 micrograms/kg, s.c.). R(+)-7-OH-DPAT (0.1-1.0 microgram) administered into the 4th cerebral ventricle dose dependently induced emesis within 1 min of dosing in ferrets. Intracerebroventricularly administered S(-)-eticlopride (0.01-1 microgram) 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 D3 receptors in the area postrema play an important role in R(+)-7-OH-DPAT-induced emesis in the ferret.
Yoshikawa
T
T
Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd., Suita/Osaka, Japan.
Yoshida
N
N
Hosoki
K
K
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004639:Emetics / Q000008:administration & dosage / Q000494:pharmacology*; D005289:Ferrets / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014628:Vagotomy; D014839:Vomiting / Q000139:chemically induced / Q000503:physiopathology*
D000932:Antiemetics; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D004639:Emetics; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C031349:7-hydroxy-2-N,N-dipropylaminotetralin