Reinitiation of sensitivity to naloxone by a single narcotic injection in postaddicted mice

D. A. Brase, E. T. Iwamoto, H. H. Loh, E. L. Way

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

In mice implanted with a morphine pellet for 3 days and subsequently withdrawn for various periods of time, a single injection of morphine results in a rapid and marked sensitization of abstinent mice to naloxone induced jumping behavior when compared to abstinent mice pretreated with saline or to placebo withdrawn mice given a single morphine injection.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 occurs at morphine doses of about 10 to 30 mg/kg and peaks at 0.5 to 2 hours after morphine administration. The ability of morphine to sensitize abstinent mice to naloxone declines with time after pellet removal and appears to consist of two components, one with a short T(0.5) and one with a much longer T(0.5). Abstinent mice are also sensitized to naloxone by levorphanol and methadone, but not by dextrorphan. It is proposed that the administration of a narcotic drug to abstinent mice uncovers a latent, pre existing state of physical dependence and restores the responsiveness of this state to naloxone.

Original languageEnglish (US)
Pages (from-to)317-325
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume197
Issue number2
StatePublished - Dec 1 1976

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