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

Abstract

The emetic action of noradrenaline was investigated in unanaesthetized 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 adminsitration 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 intracerebrocentricular 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. Finally, in cats pretreated with an intracerebroventricular injection of 5,6-dihydroxytryptamine, the emetic response to intracerebroventricular injection of noradrenaline as well as to intragastric administration of copper sulphate was not changed. It is postulated that the emesis produced by noradrenaline, injected into the cerebral ventricles, is mediated through alpha-2 adrenoceptors. These alpha-2 adrenoceptors appear to be located postsynaptically in the area postrema and they transmit emetic impulses from the area postrema to the emetic region of the brainstem reticular formation. The results obtained with reserpine and copper sulphate indicate that monoamines are involved in the regulation of vomiting in the emetic region of the brainstem reticular formation.