Chronic morphine increases the pituitary-adrenocortical response of juvenile rats to mild stress

We previously reported that chronic exposure of adult male rats to morphine by pellet implantation has no effect on corticosterone secretion but causes a marked testosterone-dependent increase in CBG. In the studies reported here, we examined the effects of chronic morphine on the pituitary-adrenocortical axis of male rats prior to the developmental rise in testosterone. In contrast to adults, morphine had little effect on CBG in peripubertal males. We found nothing remarkable with regard to basal hormone levels; morphine caused only a transient increase in ACTH and corticosterone in juveniles. However, while the pituitary-adrenocortical response to mild stress was normal in adults exposed to morphine, it was markedly increased in juveniles. After 7 days of morphine exposure, the stress response was as much as 2.5 times greater than normal in morphine-treated juveniles. This exaggerated response to stress did not appear to be due to the passive withdrawal of morphine or to an additive effect of stress plus morphine. Instead, morphine may either increase the perceived severity of stressors or decrease sensitivity to the negative feedback effects of stress levels of corticosterone in juvenile males. Either way, there is a striking shift in morphine's effects on the pituitary-adrenocortical axis across development.