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In the dog, injection of 5-hydroxytryptamine into the cerebral ventricles caused hypotension, inhibition of the pressor response to occlusion of the carotid artery and inhibition of the pressor or depressor response evoked by electrical stimulation of the central end of the cut vagus. Hypotension and inhibition of the vagal vasomotor response also occurred in dogs in which the carotid sinuses had been denervated and the vagi cut. The site of action was central. Local cerebral vascular changes could not have been responsible for the action. The central vasomotor effects of 5-hydroxytryptamine are mediated through the sympathetic outflow. Implications of these findings are discussed in relation to the effects of intravenous 5-hydroxytryptamine and the mechanism of action of reserpine.Feldberg and Sherwood (1954) studied the effects of drugs introduced into the ventricular system of cats through an implanted metallic cannula. Using a simple polyethylene cannula for injecting drugs into the lateral cerebral ventricles of dogs, we have studied the central vasomotor effects of 5-hydroxytryptamine in this species.It is generally believed that the quantity of 5-hydroxytryptamine which penetrates the bloodbrain barrier after parenteral administration is too small to produce central effects. However, a measurable rise of brain 5-hydroxytryptamine occurs on parenteral administration into mice (Shore, Pletscher, Tomich, Carlsson, Kuntzman, and Brodie, 1957). In this species an intraperitoneal injection of 5-hydroxytryptamine produces, like reserpine, general depression of muscular activity, sedation, and potentiation of the hypnotic action of barbiturates and ethanol (Shore, Silver, and Brodie, 1955). A direct inhibition of central synaptic transmission was observed by Marrazzi and Hart (1955) after the intracarotid injection of small doses of 5-hydroxytryptamine into cats, and Malcolm (1958) showed that intracarotid injection of 5-hydroxytryptamine into cats depressed the cortical response evoked by sensory nerve stimulation, but only with large doses. There are a few observations which show that 5-hydroxytryptamine, by a central action, can influence blood pressure and its responses. Bhargava and Borison (1957) found that, in cats, pressor responses elicited by threshold electrical stimulation of the medulla oblongata were depressed by large doses of 5-hydroxytryptamine given intravenously. The effect was similar to that after reserpine. Costa and Aprison (1957) observed in cross-circulation experiments that perfusion of the isolated head with 5-hydroxytryptamine caused a fall of arterial blood pressure in the recipient. A central depressor action of 5-hydroxytryptamine had previously been suggested by Ginzel and Kottegoda (1954) to explain the depressor effect obtained on its injection into the subclavian artery.The present experiments show that 5-hydroxytryptamine injected into the cerebral ventricles of dogs caused a fall in arterial blood pressure, probably due to inhibition of sympathetic vasoconstrictor tone

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Summary1. In dogs anaesthetized with pentobarbitone sodium, bradycardia with hypotension occurred on intracerebroventricular (i.c.v.) injection of noradrenaline (50-200 ,ug) or phenylephrine (100-400 ug), but tachycardia with hypotension occurred on i.c.v. injection of isoprenaline (100-200 ,ug). 2. These cardiovascular responses were central effects, and from the results obtained after bilateral vagotomy, removal of both stellate ganglia and transection of the upper cervical cord, it was evident that the efferent nervous pathway for all these effects was the sympathetic nervous system. 3. An i.c.v. injection of the a-adrenoceptor blocking agent phenoxybenzamine (10 mg) blocked the bradycardia and hypotension produced by noradrenaline or phenylephrine, and an i.c.v. injection of a /3-adrenoceptor blocking agent, either propranolol (2 mg) or N-isopropyl-p-nitrophenyl-ethanolamine (INPEA) (10 mg), blocked the tachycardia and hypotension produced by isoprenaline. 4. The cardiovascular effects produced by i.c.v. injection of the three sympathomimetic amines could be reproduced in cross-circulation experiments in the recipient dog when the amines were injected into its head circulation, and the effects of noradrenaline and phenylephrine, but not those of isoprenaline, were abolished by the a-adrenoceptor blocking agent yohimbine (1 mg/kg) injected intravenously into the donor dog. 5. It is concluded that the central a-adrenoceptors are concerned with bradycardia and the central 8-adrenoceptors with tachycardia, but that both receptors are concerned with hypotension.

1 In cats anaesthetized with chloralose, adrenoceptor and cholinoceptor agonists and antagonists were localized to the posterior hypothalamus (PH), lateral medullary pressor area (LMPA) and spinal autonomic loci to delineate the role of central cholinoceptors and adrenoceptors in cardiovascular control.2 All along the neuroaxis, the a-adrenoceptors seem to subserve an inhibitory and the f-adrenoceptors a facilitatory role in cardiovascular control. There appears to be a predominance of a-adrenoceptors at the medullary level and f-adrenoceptors at the hypothalamic level.3 The nicotinic cholinoceptors at the hypothalamic, medullary and spinal levels were facilitatory, whereas muscarinic cholinoceptors were inhibitory for cardiovascular control. However, muscarinic receptors were undetectable at the posterior hypothalamus. 4 The central cardiovascular effects of nicotine are attributed to nicotinic receptor activation and release of central catecholamines. 5 There appears to be a relationship between central cholinergic and adrenergic mechanisms in cardiovascular control.