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

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.

Behavioral and endocrine changes following antisense oligonucleotide-induced reduction in the rat NOP receptor

“…N/OFQ and NOP also appear to be directly involved in drug reinforcement, dependence and/or motivation (Devine et al 1996;Ciccocioppo et al 1998Ciccocioppo et al , 2000Malin et al 2000). While OFQ itself does not produce conditioned place preference or aversion, it does alter place conditioning produced by ethanol (EtOH) and morphine (Ciccocioppo et al 1998;Murphy et al 1999).…”

Relaxin Receptors - New Drug Targets for Multiple Disease States

“…Although Malin et al [112] found N/OFQ (i.c.v.) produced morphine-like abstinence signs, N/OFQ (i.c.v.)…”

Opioid-modulating Peptides: Mechanisms of Action

“…In naive rats, nociceptin induces abstinence-like signs in a dose dependent manner [148], and fails to precipitate withdrawal symptoms [82] or attenuate naloxone-precipitated abstinence signs [149] in morphine-dependent rats. Ueda et al [138] reported that, after a 3 day morphine treatment, mice lacking the ORL1 receptor or ddY mice receiving the antagonist J-113397 exhibit a significant reduction in naloxoneprecipitated withdrawal signs (jumps, paw tremor, backward locomotion, sniffing, defecation) in comparison to controls, suggesting that activation of the nociceptin receptor contributes to the development of physical dependence.…”