1 The purpose of the present study was to identify and investigate the role of 5‐hydroxytryptamine3 (5‐HT3) receptors in the area postrema in the control of cisplatin‐induced emesis in the ferret. 2 Homogenate binding and autoradiography experiments using the high affinity 5‐HT3 receptor ligand, (3H)‐GR65630, identified the presence of a high concentration of 5‐HT3 receptors in the area postrema of the ferret. 3 Intraperitoneal injection of the 5‐HT3 receptor antagonists, GR38032F, GR65630A and MDL72222, at doses of 1, 0.1 and 1 mg kg−1 respectively, inhibited emesis induced by cisplatin, 9 mg kg−1 i.p. 4 Discrete injection of low doses of the 5‐HT3 receptor antagonists directly into the area postrema region also inhibited cisplatin‐induced (9 mg kg−1 i.p.) emesis. The dose ranges used were: GR38032F, 0.01–1 μg; GR65630A, 0.001–0.1 μg; MDL72222, 0.1–10 μg. 5 Cisplatin‐induced emesis was not inhibited by discrete injection of ketanserin (30 μg) or methiothepin (30 μg) into the area postrema. Injection of the 5‐HT3 receptor agonist, 2‐methyl‐5‐HT, directly into the area postrema produced an incomplete emetic response. 6 These results confirm a role of 5‐HT, and in particular 5‐HT3 receptors, in the control of cisplatin‐induced emesis, and show that at least one functional site for these receptors in modulating the emetic response is the area postrema, the locus of the chemoreceptor trigger zone.
British Journal of Pharmacology – Wiley
Published: May 1, 1989
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