Nociceptin/orphanin FQ (N/OFQ) induces a quasi-morphine abstinence syndrome in the rat

D. H. Malin, J. R. Lake, W. D. Moon, D. Moy, A. L. Montellano, E. Moy, T. D. Campbell, M. V. Bell, D. Bryant, L. M. Harrison, D. K. Grandy

    Research output: Contribution to journalArticlepeer-review

    8 Scopus citations

    Abstract

    Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide that exerts antiopiate effects under some circumstances, and there is evidence that it contributes to opiate tolerance. This raises the question, might N/OFQ also contribute to opiate dependence and abstinence? Twenty-two male Sprague-Dawley rats were cannulated in the third ventricle and challenged 7 days later by third ventricle injection of 50, 200 or 1,000 ng N/OFQ or saline alone. Each rat was observed under 'blind' conditions for 30 min beginning 15 min after onset of the third ventricle injection. There was a significant positive linear trend of signs as a function of N/OFQ dose. Subjects receiving saline had 18.0±2.0 (mean±SEM) overall abstinence-like signs, whereas subjects receiving 50, 200 or 1000 ng N/OFQ had 3.5.2±3.6, 49.8±2.6 and 63.5±9.7 signs, respectively. In 16 additional rats, abstinence-like signs induced by 1000 ng N/OFQ were significantly attenuated by low SC doses of morphine or clonidine. These results raise the possibility that N/OFQ might contribute to opiate dependence and subsequent abstinence syndrome. On the other hand, N/OFQ over a wide dose range induced abstinence signs with similar potency in morphine dependent and non-dependent rats.

    Original languageEnglish (US)
    Pages (from-to)344-350
    Number of pages7
    JournalPsychopharmacology
    Volume151
    Issue number4
    DOIs
    StatePublished - 2000

    Keywords

    • Antiopiate peptides
    • Morphine
    • Nociceptin
    • Opiate abstinence syndrome
    • Opiate dependence
    • Orphanin

    ASJC Scopus subject areas

    • Pharmacology

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