A NEW APPROACH FOR ASSESSMENT OF NARCOTIC PHYSICAL DEPENDENCE USING URINARY SEX-DEPENDENT LOW MOLECULAR WEIGHT PROTEINS IN MALE RATS

Abstract

Attempts have been made to examine the relationship between urinary excretion of sex-dependent low molecular weight proteins found only in male rats (LMWP) and morphine physical dependence. Chronic administration of morphine produced a dose-related decrease in urinary LMWP excretion, which was correlated to the intensity of withdrawal signs including body weight loss and abnormal behaviors recognized after naloxone challenge. Furthermore, a statistically high correlation was obtained between the decrease in urinary LMWP excretion and the loss of body weight precipitated by naloxone challenge. LMWP was identified immunologically in the livers, kidneys, and sera using an antibody against purified LMWP. The serum level of LMWP was increased rapidly following bilateral nephrectomy. After chronic treatment with morphine, the LMWP content in the livers, kidneys, and sera were decreased. These findings indicate that the decrease in urinary LMWP excretion induced by chronic administration of morphine can be a useful parameter to assess the development of physical dependence on narcotics on the peripheral level without requiring drug withdrawal and naloxone challenge. This decrease in urinary LMWP may be caused by the inhibition of LMWP synthesis in the liver.