NO RELATION OF PLASMA MORPHINE LEVEL TO THE SEVERITY OF NALOXONE-INDUCED WITHDRAWAL IN ACUTE MORPHINE-DEPENDENT RATS

Plasma morphine concentration and naloxone-precipitated withdrawal bod y weight loss and plasma corticosterone (PCS) increase were determined at 12, 18 and 24 hr after i.v. infusion of morphine at a constant rat e of 10 mg/kg/hr for 4 hr in Sprague-Dawley rats. Plasma morphine conc entration declined 98.0% within 12 hr and further declined 58.8% durin g 12-24 hr after morphine infusion. There was a significant difference between plasma morphine concentrations at 12 and 24 hr after the morp hine infusion. Naloxone (0.5 and 2.0 mg/kg)-precipitated withdrawal, b ut not spontaneous withdrawal, was elicited at 12-24 hr after the morp hine infusion, and the severity of withdrawal precipitated by 2.0 mg/k g naloxone was the same at 12-24 hr after the morphine infusion. Furth ermore, there was no significant correlation between plasma morphine c oncentration 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-precipi tated withdrawal is not related to the plasma morphine concentration a t the time of naloxone injection, that is, the rate of morphine remova l from its receptor sites.