Effects of morphine on central catecholamine turnover, blood pressure and heart rate in the rat

In the unanaesthetized rat morphine caused increased dopamine (DA) turnover, unchanged or possibly increased central noradrenaline (NA) turnover (utilization), hypertension and tachycardia. In the anaesthetized rat, brain DA turnover was not affected, whereas the NA-turnover was decelerated, particularly in some brain regions, e.g. cerebral cortex and medulla oblongata, and hypotension and bradycardia was obtained. Both biochemical and cardiovascular effects of morphine were antagonized by naloxone. A very small dose of morphine (1 mg/kg) caused tachycardia also in the anaesthetized rat. Decerebration just inferior to the inferior colliculus abolished the conscious rat, but left the circulatory, depressant actions of the drug unchanged. The morphine-induced cardiovascular effects, particularly the hypotension and bradycardia in the anaesthetized animal, are suggested to be related to, or mediated by, the effects of the drug on brain NA-mechanisms, especially in view of several similarities between morphine and the antihypertensive alpha-adrenergic agonist clonidine. Whereas higher brain structures appear important in the excitatory, circulatory effects of morphine, structures below the decerebration level, e.g. medulla oblongata, appear primarily involved in the hypotension and bradycardia obtained in the anaesthetized animal. Possibly, morphine has a diphasic dose-response curve with respect to cardiovascular function and, by inference, on brain noradrenergic mechanisms.