STUDIES ON THE MECHANISM OF STIMULATION OF ACTH SECRETION WITH THE AID OF MORPHINE AS A BLOCKING AGENT1

Abstract

Effect of morphine on ACTH secretion in response to a number of stressful stimuli was shown in rats anesthetized with sodium pentobarbital. When such rats were given morphine none of the stimuli tested, e.g., administration of histamine, epinephrine, or vasopressin, laparotomy, or unilateral adrenalectomy, resulted in an increased rate of secretion of ACTH, although the stimuli were effective in anesthetized control rats. Ten times the minimal effective dose of histamine for control rats was required in order to produce a significant fall in adrenal ascorbic acid concentration in rats treated with morphine. Observations on unanesthetized rats, conditioned by 4 daily injections, demonstrated that morphine alone, i.e., without sodium pentobarbital, was capable of inhibiting the response of the anterior pituitary to the usual effect of histamine. Whether they had been pre-treated with morphine or not, there was no significant difference in the adrenal ascorbic acid response of hypophysectomized rats anesthetized with sodium pentobarbital to a standard dose of ACTH. This clearly demonstrates that morphine does not interfere directly with the response of the adrenal cortex to ACTH. The acute effect of stressful stimuli on the rate of ACTH secretion is not mediated by a decrease in the concentration of circulating adrenal cortical hormones or by histamine, epinephrine, or vasopressin acting directly upon the anterior pituitary. Rather, the results are intrepreted in support of the hypothesis that the hypothalamus is an essential component of the mechanism of acute stimulation of ACTH secretion. A method utilizing morphine-treated rats was suggested for the detection and biological assay of the postulated hypothalamic neurohormone, and evidence that the hormone is not histamine, epinephrine, or vasopressin was presented.