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 35.2±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.
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Malin, D., Lake, J., Moon, W. et al. Nociceptin/orphanin FQ (N/OFQ) induces a quasi-morphine abstinence syndrome in the rat. Psychopharmacology 151, 344–350 (2000). https://doi.org/10.1007/s002130000473
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DOI: https://doi.org/10.1007/s002130000473