THE ROLE OF ALPHA-ADRENERGIC MECHANISMS WITHIN THE AREA POSTREMA IN DOPAMINE-INDUCED EMESIS

Intracerebroventricular injection of dopamine (0.5-4.0 mg) produced do se-dependent and short-lasting emesis (1-8 min) in cats, which was abo lished after ablation of the area postrema. Relatively selective alpha (2)-adrenoceptor antagonists (yohimbine and idazoxan) and a mixed alph a(1)- and alpha(2)-adrenoceptor antagonist (tolazoline), but not a non -selective alpha(1)-adrenoceptor antagonist (prazosin), injected intra cerebroventricularly inhibited the emesis induced by intracerebroventr icular dopamine. However, dopamine receptor antagonists (chlorpromazin e, droperidol, spiperone, domperidone, triflupromazine, sulpiride and metoclopramide), an antimuscarinic drug (atropine), a ganglionic block ing agent (mecamylamine), an opioid receptor antagonist (naloxone) and a 5-HT receptor antagonist (methysergide), all injected intracerebrov entricularly, had no significant effect on emesis evoked by intracereb roventricular dop amine. The emetic response to intracerebroventricula r dop amine was attenuated in cats pretreated with intracerebroventric ular reserpine, 6-hydroxydopamine, alpha-methyl-p-tyrosine and hemicho linium-3. It is postulated that dopamine-induced emesis is mediated th rough the release of noradrenaline acting at alpha(2)-adrenoceptors an d that it depends on the integrity of monoaminergic and possibly choli nergic structures within the area postrema. It appears, therefore, tha t the emetic effect of intracerebroventricular dopamine is mediated by adrenergic rather than dopaminergic mechanisms in the area postrema, at least in the cat.