TOLERANCE TO MORPHINE. I. EFFECTS ON CATECHOLAMINES IN THE BRAIN AND ADRENAL GLANDS

In dogs, rats and rabbits large doses of morphine caused less sedation than smaller doses but greater decreases in brain stem norepinephrine and adrenal catecholamines. Animals made tolerant to the sedative action of morphine by the subchronic administration of drug had normal levels of brain and adrenal catecholamines. After the administration of large doses of morphine for 60 to 100 days, brain and adrenal catecholamines were supranormal. The administration of a monoamine oxidase inhibitor (1-phenyl-2-hydrazinopropane) caused a significantly greater increase in brain norepinephrine in morphine-tolerant than in control rats. The injection of nalorphine into morphinetolerant dogs and rabbits produced excitatory "abstinence" syndromes accompanied by decreases in brain norepinephrine and adrenal epinephrine. In the rat the "abstinence" syndrome consisted of sedation and hypothermia, and brain and adrenal catecholamines did not decrease. Morphine-tolerant dogs anesthetized with pentobarbital prior to the injection of nalorphine failed to show changes in brain or adrenal catecholamines. The findings are discussed in the light of the possibilities that brain norepinephrine functions as part of the sympathetic nervous system and that its release is accompanied by arousal or excitement.