Alterations in the efficacy of naloxone induced by stress, cyclic adenosine monophosphate, and morphine tolerance.

Pretreatment of mice with a single injection of morphine or by chronic implantation of morphine pellets increased the ability of naloxone to antagonize the analgetic effects of morphine. However, this increased effectiveness of naloxone was also produced by pretreatment with diethylether, ACTH, corticosterone or dexamethasone. Thus, the increased potency of naloxone observed after pretreatment with narcotics may be due, at least in part, to those pretreatments on the pituitary--adrenal axis. In addition, in animals made highly tolerant and dependent by cAMP administration during morphine pellet implantation, the narcotic antagonist potency of naloxone was similar to that of untreated animals.