REINITIATION OF SENSITIVITY TO NALOXONE BY A SINGLE NARCOTIC INJECTION IN POST-ADDICTED MICE

Abstract

In mice implanted with a morphine pellet for 3 days and subsequently withdrawn for various periods of time, a single injection of morphine resulted in a rapid and marked sensitization of abstinent mice to naloxone-induced jumping behavior when compared to abstinent mice pretreated with saline or to placebo-withdrawn mice given a single morphine injection. Maximum sensitization of abstinent mice occurred at morphine doses of about 10-30 mg/kg and peaked at 0.5-2 h after morphine administration. The ability of morphine to sensitize abstinent mice to naloxone declined with time after pellet removal and appeared to consist of 2 components, 1 with a short half-life [T1/2] and 1 with a much longer T1/2. Abstinent mice were also sensitized to naloxone by levorphanol and methadone, but not by dextrorphan. The administration of a narcotic drug to abstinent mice uncovered a latent, pre-existing state of physical dependence and restored the responsiveness of this state to naloxone.