Effects of adrenoceptor blocking agents on body temperature

1. The effect on rectal temperature of adrenoceptor blocking agents, injected through a cannula chronically implanted into a lateral cerebral ventricle, was examined in unanaesthetized rabbits, cats and rats, kept at room temperature (19-22 degrees C).2. In rabbits, the alpha-adrenoceptor blocking agent phenoxybenzamine (50 or 100 mug) produced marked hypothermia when injected intraventricularly but not when injected intravenously. In some rabbits as little as 1 mug was effective on intraventricular injection. Phentolamine and ergotamine, the other alpha-adrenoceptor blocking agents examined, had a much weaker hypothermic action when injected intraventricularly, whereas the beta-adrenoceptor blocking agents propranolol, pronethalol and Trasicor had no effect.3. In rabbits in which the noradrenaline stores of the hypothalamus were depleted by intraventricular injections of reserpine, the hypothermic effect of phenoxybenzamine was abolished and remained abolished for a few days.4. In cats, an intraventricular injection of phenoxybenzamine (200 mug) produced long-lasting hyperthermia, but not in all cats, and only with the first, or the first two or three injections. Injected intraperitoneally, this dose had no effect on temperature. Phentolamine (100 or 200 mug) had a very weak hyperthermic effect and phentolamine (500 mug), a hypothermic effect, but only on intraventricular injection, whereas ergotamine (100 and 200 mug) had a weak hyperthermic effect both on intraventricular and intraperitoneal injection. Propranolol and Trasicor had no effect on temperature when injected intraventricularly.5. In rats, phenoxybenzamine (5 or 20 mug) produced long-lasting hypothermia on intraventricular injection.6. Some of the temperature effects produced by intraventricular injections of the alpha-adrenoceptor blocking agents are explained on the assumption that they prevent the effect on temperature produced by a continuous release of noradrenaline from adrenergic neurones innervating the anterior hypothalamus.