Jpn. J. Pharmacol. 69, 187-193 (1995)

No Relation of Plasma Morphine Level to the Severity of Naloxone-Induced Withdrawal in Acute Morphine-Dependent Rats

Shiroh Kishioka, Norihiro Inoue, Shigeru Nishida, Yuko Fukunaga and Hiroyuki Yamamoto

Departments of Pharmacology, Wakayama Medical College, 9-Bancho 27, Wakayama 640, Japan

Abstract: Plasma morphine concentration and naloxone-precipitated withdrawal body weight loss and plasma corticosterone (PCS) increase were determined at 12, 18 and 24 hr after i.v. infusion of morphine at a constant rate of 10 mg/kg/hr for 4 hr in Sprague-Dawley rats. Plasma morphine concentration declined 98.0% within 12 hr and further declined 58.8% during 12-24 hr after morphine infusion. There was a significant difference between plasma morphine concentrations at 12 and 24 hr after the morphine infusion. Naloxone (0.5 and 2.0 mg/kg)-precipitated withdrawal, but not spontaneous withdrawal, was elicited at 12-24 hr after the morphine infusion, and the severity of withdrawal precipitated by 2.0 mg/kg naloxone was the same at 12-24 hr after the morphine infusion. Furthermore, there was no significant correlation between plasma morphine concentration and body weight loss or PCS increase. The results suggest that a constant degree of morphine dependence is sustained during 12-24 hr after the morphine infusion and the severity of naloxone-precipitated withdrawal is not related to the plasma morphine concentration at the time of naloxone injection, that is, the rate of morphine removal from its receptor sites.

Keywords: Intravenous morphine infusion, Plasma morphine concentration, Naloxone-withdrawal, Body weight loss, Plasma corticosterone increase

Copyright© The Japanese Pharmacological Society 1995

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