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

• Published in: Psychopharmacologia Vol. 151; no. 4; pp. 344 - 350
• Main Authors: MALIN, David H, LAKE, J. Ronald, GRANDY, David K, MOON, William D, MOY, Debora, MONTELLANO, Ana L, MOY, Edward, CAMPBELL, Tracy D, BELL, Maurice V, BRYANT, Dana, HARRISON, Laura M
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.09.2000
• Subjects: abstinence syndrome; Animals; Biological and medical sciences; Clonidine - pharmacology; Dose-Response Relationship, Drug; Drug addictions; Drug toxicity and drugs side effects treatment; Male; Medical sciences; Morphine - adverse effects; Morphine Dependence - drug therapy; Nociceptin; Opioid Peptides - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome - etiology; Toxicity: nervous system and muscle; Toxicology; Drug addiction; Nervous system diseases; Rat; Toxicity; Rodentia; Detoxification; Central nervous system; Morphine; Opiates; Narcotic analgesic; Neuropeptide; Abstinence; Biological activity; Dose activity relation; Vertebrata; Mammalia; Animal; Dependence; Intracerebral administration; Subcutaneous administration; Drug of abuse; Withdrawal syndrome; Brain (vertebrata)
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130000473

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.