QUANTITATIVE PROPERTIES OF PLASMA-CORTICOSTERONE ELEVATION INDUCED BYNALOXONE-PRECIPITATED WITHDRAWAL IN MORPHINE-DEPENDENT RATS

Elevation of plasma corticosterone (PCS) has been used as an indicator of morphine withdrawal, but it is not clear whether the magnitude of elevation is related to the intensity of the dependence. The dose-depe ndent effects of naloxone on PCS and body weight were studied in male Sprague-Dawley rats rendered physically dependent on morphine by injec ting increasing doses of 40-120 mg/kg/day, s.c. twice daily for 1-6 da ys. Naloxone (0.01-2.0 mg/kg, s.c.) was administered 3 hr after the la st morphine administration. Naloxone elevated PCS levels in a dose-dep endent manner in all groups treated with morphine, and the elevation w as correlated with the number of days of morphine treatment. Naloxone also reduced dose-dependently the body weight in all groups treated wi th morphine; in this case, a reverse correlation was obtained between the body weight changes and the PCS levels. It was confirmed that PCS elevation is a quantitative sign of naloxone-precipitated morphine wit hdrawal and that the elevation is indicative of the degree of morphine physical dependence.