Endocrine influences on the actions of morphine. I. Alteration of target gland hormones.

There are few data concerning the effects of hormones on opiate actions. Consequently, we have studied the influences of peripheral endocrine systems upon sensitivity and tolerance to three major morphine effects: antinociception, hypothermia and catalepsy. It was found that in opiate naive animals adrenalectomy increased morphine-induced antinociception, hypothermia and catalepsy, whereas dexamethasone treatment decreased all three opiate effects. Thyroidectomy decreased the antinociceptive and cataleptic actions of morphine, but had no effect on the hypothermic response. Thyroxine treatment markedly altered the temperature response to morphine without affecting the other two actions. Control animals showed both hyperthermia and hypothermia after morphine, but animals treated chronically with thyroxine showed only hyperthermia. Alterations of the gonadal axis in males had no pronounced effects upon the actions of morphine. Further investigations demonstrated that morphine, when administered i.c.v. to thyroidectomized animals, produced responses similar to those seen after s.c. administration. During chronic studies, the only notable effects of endocrine alterations on the development of tolerance to morphine were trends toward suppression with dexamethasone treatment and trends toward augmentation after adrenalectomy. These results indicate that the actions of morphine are influenced by endocrine status. Adrenal hormones exert their effects upon the actions of morphine via peripheral metabolic alterations, whereas the effects of thyroid hormones are mediated at central sites. These results also indicate that the development of tolerance to morphine is not significantly influenced by any of the endocrine systems studied.