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Neurosci Lett. 1997 Nov 21;237(2-3):136-8.

Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene.

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Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, Japan.


In mice lacking the nociceptin (or orphanin FQ) receptor gene, when 10 mg/kg of morphine was subcutaneously given, a potent analgesia in the tail pinch test was observed. The analgesic effect of morphine was equivalent among wild-type, heterozygous and homozygous mutant mice. When morphine was given to such mice in a dose of 10 mg/kg once per day for 5 days, wild-type and heterozygous mice showed marked tolerance or reduction in the morphine analgesia on the 5th day, while homozygous mice showed only 50% reduction in the peripheral analgesia of morphine. These findings suggest that nociceptin or its receptor plays important roles in the in vivo mechanism for the development of morphine tolerance.

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