Availability of serum corticosterone level for quantitative evaluation of morphine withdrawal in mice

Physical dependence on morphine is evidenced by the withdrawal syndromes, including body weight loss, which are induced by the discontinuation of morphine exposure or by the treatment with naloxone, an opioid receptor antagonist. The present study was designed to examine whether the elevation of serum corticosterone (SCS) level induced by naloxone-precipitated morphine withdrawal was a useful index to quantify the physical dependence on morphine in mice, which was compared with body weight loss induced by naloxone-precipitated morphine withdrawal. The SCS level was dependent on the dosage and the number of dosing of morphine and challenging dosage of naloxone. Intraplantar injection of formalin, potentially producing inflammatory pain, inhibited both body weight loss and SCS increase induced by naloxone challenge in mice receiving repeated exposure of morphine, indicating that formalin-induced pain attenuated the development of physical dependence on morphine. The magnitude of body weight loss in morphine withdrawal was significantly correlated with the magnitude of naloxone challenge-induced SCS increase. These results suggest that the naloxoneinduced increase in SCS level is a quantitative index of the magnitude of physical dependence on morphine in mice.