HYPOTHALAMO-PITUITARY-ADRENOCORTICAL (HPA) FUNCTION IN THE MORPHINE-DEPENDENT RAT

Morphine dependence was induced by ten daily administrations of morphine with gradually increasing dosage (40~160 mg/kg/day s.c.) to male Sprague-Dawley rats, the dosage being divided in 2/day for the first 8 days and 4/day for the last 2 days. Diurnal variation in body weight in morphine dependent rats was the same as in naive rats. Although body temperature in the naive rats showed a diurnal variation with the highest at 3:00 and the lowest at 15:00, in the morphine dependent rats there was no distinct variation. Plasma corti-costerone level (PC) in naive rats showed diurnal variation with the peak at 21:00 and the trough at 9:00. PC in morphine dependent rats showed the same diurnal variation as did the naive rats, while such disappeared following pentobarbital anesthesia (80 mg/kg i.p. for 45 min) and PC was low all during the day. The PC increase following formalin administration to morphine dependent rats was higher than in naive rats. 0.1 mg/kg s.c. of dexamethasone completely inhibited PC increase after formalin in naive rats, but the dexamethasone inhibition in morphine dependent rats was not complete even with a larger dose, i.e. 10 mg/kg s.c. Diurnal variations and other differences were not detected in the adrenal response to ACTH (in vivo, in vitro) between naive and morphine dependent rats. These results suggest that HPA function takes part in the development of morphine dependence. © 1979, The Japanese Pharmacological Society. All rights reserved.