Chronic exposure to morphine decreases physiologically active corticosterone in both male and female rats but by different mechanisms.

We previously reported that chronic exposure of male rats to morphine markedly increases the concentration of corticosteroid-binding globulin (CBG) in blood. This in turn appears to greatly reduce the amount of corticosterone available to intracellular receptors. In the study reported here, we found that in contrast to the effect in males, morphine has no apparent effect on CBG in females. This pronounced sex difference does not appear to be attributable to differences in morphine pharmacokinetics, short-term actions of gonadal hormones in adulthood or sex differences in CBG or corticosterone levels. In any case, it is evident that morphine does not decrease the level of physiologically active corticosterone through CBG in females as it appears to do in males. On the other hand, we also found a distinct sex difference with regard to the effects of morphine on corticosterone. Chronic exposure to morphine had no apparent effect on corticosterone levels in males but resulted in markedly lower levels in females. Thus, morphine appears to cause a deficit in physiologically active corticosterone in both sexes but by different mechanisms.