Abstract

This study was designed to evaluate systematically the effects of stress on actions of exogenously administered opioids. Dose- and time-dependent analgesic (tail-flick) and thermic (core body temperature) effects of morphine and methadone were determined in unstressed rats and in rats exposed to the stress of restraint or a cold environment. To assess the role of the pituitary-adrencortical axis in stress-opioid interactions, tests were performed in hypophysectomized and pituitary-intact rats. The analgesic effect of morphine was greater in all stressed groups than in unstressed controls and was greater still in all groups of hypophysectomized rats than in corresponding groups of intact animals. The analgesic effect of methadone was also greater in all groups of stressed as compared to unstressed rats but was not modified by hypophysectomy, in contrast to the situation with morphine. The effects of both opioids on body temperature varied quantitatively and qualitatively as a function of dose, conditions under which the animals were tested and presence or absence of the pituitary gland. Doses that increased temperature in unstressed pituitary-intact rats decreased temperature in unstressed hypophysectomized rats and in all stressed rats. Brain and plasma levels of morphine were comparable in stressed and unstressed pituitary-intact rats, but were significantly higher in unstressed hypophysectomized animals. Thus, hypophysectomy-induced potentiation of the analgesic effect of morphine is probably due to pharmacokinetic factors whereas stress-induced potentiation of opioid analgesia appears to be a distinct phenomenon, one that is independent of the pituitary-adrencortical axis and general for the pharmacologic class of morphine-like drugs. The well-documented hypothermic response of restrained rats to doses of opioids that increase or have no affect on the body temperature of unrestrained animals appears to represent another example of stress-induced potentiation of opioid effects.