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

Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide that exerts antiopiate eff ects 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 ven tricle 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 t rend 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 r eceiving 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 in duced by 1000 ng N/OFQ were significantly attenuated by low SC doses of mor phine or clonidine. These results raise the possibility that N/OFQ might co ntribute to opiate dependence and subsequent abstinence syndrome. On the ot her hand, N/OFQ over a wide dose range induced abstinence signs with simila r potency in morphine dependent and non-dependent rats.