[Withdrawal characteristics following frequent intravenous administration of several opioids in rats]

Characteristics of withdrawal signs of several opioids were compared in rats after short-term frequent intravenous infusions. Male Sprague-Dawley rats with catheters implanted in the jugular veins were infused with a fixed dose of a drug hourly for 72 hrs. Thirty min after the final infusion, naloxone 4 mg/kg, s.c. was administered and withdrawal signs were observed for 1 hr and the severity of the withdrawal signs was scored, classified into a behavioral sign score, autonomic sign score, and body weight loss score. As a result, total withdrawal scores of morphine, methadone, d-propoxyphene, loperamide, tramadol, and pentazocine were significantly higher than that of saline, with the highest score being observed for 4 mg/kg or more of morphine. The total score of ethylketocyclazocine was slightly but significantly higher than that of saline. Buprenorphine and thebaine produced no observable withdrawal signs. The behavioral sign score tended to be higher than the other 2 scores in the drugs showing relatively low but significant total scores such as tramadol, pentazocine, and ethylketocyclazocine, while the score of autonomic signs or the body weight loss tended to be higher in drugs showing high total scores. Thus, in the case of opioids, it is considered that the severity of withdrawal signs was mainly derived from the autonomic signs including diarrhea which may result in body weight loss.