ONTOGENIC STUDIES OF TOLERANCE DEVELOPMENT - EFFECTS OF CHRONIC MORPHINE ON THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

Endogenous opiates are important regulators of the hypothalamic-pituit ary-adrenal (HPA) axis in rats, Tolerance clearly develops to morphine -induced stimulation of the HPA axis in adult rats (Ignar and Kuhn 199 0), The goal of the present study was to determine whether tolerance t o morphine-induced stimulation of the HPA axis developed in neonatal a nd weanling rats treated chronically with morphine. Rats were injected with morphine or saline between days 4-8 postnatal (pups) or days 21- 25 (weanlings) and tolerances assessed by determining dose-response cu rves for ACTH and-corticosterone secretion following an acute morphine challenge. Weanlings displayed marked tolerance to the stimulation of ACTH and corticosterone secretion by morphine, Tolerance was also obs erved in pups to morphine-stimulated ACTH and corticosterone release, These findings suggest that the relative adaptability of the HPA axis to chronic morphine in neonatal and weanling rats is similar.