Tolerance to morphine. III. Effects on catecholamines in the heart, intestine and spleen.

The administration to rats of large doses of morphine caused decreases in the norepinephrine content of the intestines and the spleen. Cardiac norepinephrine was decreased only in animals which convulsed. Nonconvulsant doses of morphine increased the concentration of catecholamines in the heart. A large part of the increase was epinephrine, which was presumed to have been accumulated by the heart after release from the adrenal medulla. After the administration of 10 doses of morphine the heart, intestine and spleen contained normal amounts of norepinephrine. The chronic administration of morphine led to decreases in cardiac, intestinal and splenic norepinephrine. That these decreases were not related to an impairment of the synthesis of norpinephrine was indicated by the fact that the administration of an amine oxidase inhibitor (JB-516) caused as large an increase in cardiac and splenic norepinephrine as occurred in control rats. The decreased norepinephrine levels were returned approximately to normal by the administration of nalorphine. The results are discussed in relation to the effects of morphine on brain and adrenal catecholamines and to morphine tolerance and physical dependence.