Abstract
Rats were medicated by continuous infusion through an indwelling intraperitoneal cannula. Physical dependence on morphine was rapidly produced. In precipitated withdrawal tests after 2 days of morphine infusion of 100 mg/kg/24 hours, as little as 0.1 mg/kg of naloxone or 1 mg/kg of nalorphine-precipitated abstinence. Abrupt withdrawal after 6 days of high-dose morphine infusion, using either an escalating dose schedule (50 mg/kg/24 hr on day 1, 100 mg/kg/ 24 hr on day 2 and 200 mg/kg/24 hr on days 3-6) or a constant-dose infusion of 100 mg/kg/24 hr, resulted in a marked abstinence syndrome. Demonstrable physical dependence was produced with doses of morphine as low as 12.5 mg/kg/24 hr for 6 days. Continuous infusion allowed the demonstration of primary physical dependence on codeine and meperidine by abrupt withdrawal as well as precipitated withdrawal. Suppression of morphine abstinence by methadone, codeine or meperidine substitution in both weakly and strongly morphine-dependent rats was demonstrated.
Footnotes
- Received July 26, 1973.
- Accepted May 17, 1974.
- © 1974 by The Williams & Wilkins Co.
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