Further studies on nicotine-induced emesis: nicotinic mediation in area postrema.

In unanesthetized cats the emetic action of an injection of nicotine into the cerebral ventricle through chronically implanted cannulae was investigated. Nicotine injected in doses of 0.02-1.0 mg produced dose-dependent vomiting, which was abolished after ablation of the area postrema. However, copper sulfate given intragastrically evoked vomiting in cats with an ablated area postrema. The emetic response to intracerebroventricular (ICV) nicotine as well as the vomiting produced by intragastric copper sulfate was depressed or abolished in cats pretreated with ICV reserpine. On the other hand, the emetic response to ICV nicotine and to intragastric copper sulfate was virtually unchanged in cats pretreated with ICV 6-hydroxydopamine and 5,6-dihydroxytryptamine. The duration of vomiting produced by intragastric copper sulfate, but not that of ICV nicotine, was potentiated in cats pretreated with hemicholinium-3. Ganglionic blocking agents, mecamylamine and hexamethonium, injected ICV prevented the vomiting elicited by ICV nicotine. On the other hand, selected anti-muscarinic drugs, alpha and beta adrenergic receptor antagonists, dopamine antagonists, antihistamines and a 5-hydroxytryptamine antagonist all injected into the cerebral ventricle had virtually no effect on the vomiting induced by ICV nicotine. It is postulated that nicotine evokes vomiting by its action on nicotinic receptors within the area postrema but not on catecholaminergic or serotonergic neurones. Finally, acetylcholine could also be involved in the inhibition of the complex mechanisms underlying the central regulation of vomiting.