Abstract

We have previously reported that morphine inhibits Concanavalin A-stimulated blood lymphocyte proliferation in a dose-dependent manner. Maximal (80%) inhibition by morphine occurred with a dose of 10 mg/kg 2 hours after drug administration. Concurrent with this suppressive effect was a 2- to 4-fold increase in plasma corticosterone concentrations. In the present study, we examined the potential contribution of the hypothalamic-pituitary-adrenal axis to the suppressive effects of acute morphine exposure. To assess the role of glucocorticoids, rats were pretreated with the steroid receptor antagonist RU486 (20 mg/kg) 30 min before morphine (10 mg/kg) administration. A significant inhibition of lymphocyte activity occurred with morphine in the absence or presence of RU486 pretreatment. Consistent with a mechanism independent of glucocorticoids, adrenalectomy also failed to attenuate the inhibitory actions of morphine. To examine the potential role of pituitary hormones in the suppressive effect, similar experiments were carried out in hypophysectomized animals. In sham-operated or hypophysectomized animals, morphine was found to be equally effective in suppressing lymphocyte proliferation. These results suggest that factors elaborated from intact pituitary or adrenal glands are not required for the acute inhibitory effects of morphine on peripheral blood lymphocyte activity.