Involvement of the area postrema and the nucleus tractus solitarius in the emetogenic action of emetine in rats

Abstract

ObjectivesThe aim of the present study was to demonstrate the effective dose of emetine for inducing nausea and/or emesis, and the effects of emetine on the excitability of central neurons in the area postrema (AP) and the nucleus tractus solitarius (NTS). MethodsRats were used as experimental animals. We measured the conditioned taste aversion (CTA) induced by the intraperitoneal administration of emetine solution (0.03, 0.1, 0.3, 0.5, and 1.0 mM in saline) and that of only saline. We also performed immunohistochemical analyses of c-Fos expression in the area postrema and the NTS, to examine changes in the excitability of brainstem neurons that may be responsible for emetine-induced nausea and/or emesis. ResultsThe emetine-induced CTA occurred in a dose-dependent manner. The half maximal inhibitory concentration (IC50) of emetine on the saccharin preference was calculated to be 0.348 mM using the Hill equation. In the animals injected with emetine (0.5 and 1.0 mM), many c-Fos-like immunoreactive (Fos-ir) cells were observed in the area postrema and the NTS, while few Fos-ir cells were identified in the animals injected with saline. The average number of Fos-ir cells in the area postrema and the NTS was significantly larger in animals injected with emetine than in animals injected with saline. ConclusionsThe present study demonstrated a dose-responsive manner of emetine effects and emetine-induced upregulation of neuronal excitability in the area postrema and the NTS that form a part of the induction mechanisms of emetine-induced nausea and/or emesis.