Study of some of the Pharmacological Actions of Noradrenaline and Related Compounds Injected into the Brains of Mice

Abstract

A study has been made of the actions of noradrenaline when injected into the cerebral ventricles of conscious mice. Wherever possible, measurements have been placed on an objective basis, and comparison with related compounds has been carried out where appropriate. The actions of centrally injected catecholamines have been reviewed, and the current status of noradrenaline as a central transmitter agent is discussed. Intraventricular injection of noradrenaline induced a characteristic syndrome, of which hypothermia and depression of locomotor activity were the predominant characteristics. consciousness was not impaired at any dose level, although analgesia could be elicited under appropriate experimental conditions. These effects resembled the known actions of noradrenaline on peripheral alpha receptors, both in the order of potency of the catecholamines and in sensitivity to drugs and were absent after peripheral injection of noradrenaline. Evidence has been adduced to support the hypothesis that the hypothermic actions of noradrenaline, accompanied by a fall in metabolic rate and by cutaneous vasodilation, may be due to an integrated stimulation of heat-loss mechanisms. It is suggested that this could be a direct effect of noradrenaline, since no evidence could be found that noradrenaline could induce a false ‘heat-load’ signal from hypothalamic thermodetectors, such as might be predicted to follow cerebral vasoconstriction. The possible transmitter function of noradrenaline in the central control of body temperature has been discussed. The analgesic actions of noradrenaline depended upon the test situation used. Evidence has been found that noradrenaline may induce analgesia by activation of cholinergic mechanisms, and it could have a physiological role in the modulation of sensory transmission, particularly in reference to the perception of pain. Evidence from behavioural studies, and from a study of the action of drugs on nonadrenaline-induced reduction in exploratory locomotor activity, suggests that noradrenaline may possess intrinsic ‘excitant’ activity on behaviour, coexistent with the above-mentioned ‘depressant’ actions. The importance of such dual activity has been discussed, with special reference to the known effects of centrally injected noradrenaline in other species.