Noradrenaline-induced emesis. Alpha-2 adrenoceptor mediation in the area postrema

The emetic action of noradrenaline was investigated in unanesthetized cats, after it was injected into the cerebral ventricles through chronically implanted cannulae. Intracerebroventricular injection of noradrenaline produced dose-dependent and shortlasting emesis, which was abolished after ablation of the area postrema. However, copper sulphate, given orally, evoked emesis in cats with an ablated area postrema. The selective alpha-2 adrenoceptor antagonist, yohimbine, as well as the mixed alpha-1 and alpha-2 adrenoceptor blocking drugs, phentolamine, tolazoline, phenoxybenzamine and dihydroergotamine, but not the selective alpha-1 adrenoceptor antagonist, prazosin, all injected into the cerebral ventricles, attenuated or blocked the emesis evoked by intracerebroventricular injection of noradrenaline. Of the alpha-adrenoceptor antagonist, only yohimbine produced dose-dependent inhibition of the emesis induced by noradrenaline. On the contrary, selected beta-adrenoceptor blocking agents, an antimuscarinic drug, a ganglionic blocking agent, an antihistamine, dopamine antagonists and a 5-hydroxytryptamine antagonist, all injected into the cerebral ventricles, had no significant effect on the emesis induced by noradrenaline, similarly injected. The emetic response to intracerebroventricular injection of noradrenaline, as well as to intragastric administration of copper sulphate was not altered in cats pretreated with intracerebroventricular injections of alpha-methyl-p-tyrosine and bretylium. On the other hand, the emetic response to intracerebroventricular injection of noradrenaline and to intragastric administration of copper sulphate was attentuated or blocked in cats pretreated with reserpine intracerebroventricularly. Moreover, in cats pretreated with intracerebroventricular injection of 6-hydroxydopamine and hemicholinium, the emesis induced by intracerebroventricular administration of noradrenaline but not that produced by intragastric injection of copper sulphate, was depressed.(ABSTRACT TRUNCATED AT 250 WORDS)