Loss of sensitivity to morphine induced by prolonged ACTH treatment

The effect of long term ACTH treatment on some actions of morphine were studied. The effect of ACTH administration was compared to that induced by acute dexamethasone injection. ACTH caused a delayed inhibition of the morphine induced increase in growth hormone secretion demonstrable 24 hr after the last hormone injection. The morphine induced increase of striatal DOPAC (3,4-dihydroxyphenylacetic acid) content was also inhibited by ACTH treatment, however, neither the analgesia, nor the hypermotility caused by morphine were affected. Dexamethasone did not alter significantly the responsiveness to morphine. It is concluded that the prolonged exposure to ACTH presumably causes a corticosterone-mediated loss of responsiveness of functionally restricted opiate sensitive mechanisms in the central nervous system.