Attenuation of ethanol self-administration and of conditioned reinstatement of alcohol-seeking behaviour by the antiopioid peptide nociceptin/orphanin FQ in alcohol-preferring rats.

摘要

Rationale: Nociceptin/orphanin FQ (N/OFQ),\udthe endogenous ligand of the opioid-like orphan receptor\udNOP, was shown to reduce home-cage ethanol consumption,\udethanol-induced conditioned place preference and\udstress-induced reinstatement of alcohol-seeking behaviour.\udObjectives: The present study, using genetically\udselected Marchigian Sardinian alcohol-preferring (msP)\udrats, was designed to evaluate the effect of this opioid\udpeptide on 10% ethanol and 10% sucrose self-administration,\udunder a fixed-ratio 1 (FR 1) or a progressive-ratio\ud(PR) schedule of reinforcement. Furthermore, using an\udexperimental model of relapse in which rats were trained\udto lever press for ethanol in the presence of the\uddiscriminative stimulus of an orange odour (S+) and a\ud1-s cue light (CS+) or for water in the presence of anise\udodour (S) and 1-s white noise (CS), the effect of N/oFQ\udon cue-induced reinstatement of extinguished ethanol\udresponding was investigated. \udResults: Sub-chronic (6 days) intracerebroventricular (i.c.v.) injection of 0.5 mg or 1.0 mg N/OFQ per rat significantly reduced alcohol self-administration under both the FR 1 and PR schedules of reinforcement. Conversely, i.c.v. administration of 0.5, 1.0 or 4.0 mg of the peptide per rat did not affect sucrose self-administration. In addition, i.c.v. N/\udOFQ (1.0–2.0 mg per rat) significantly inhibited the\udreinstatement of extinguished ethanol responding under\udan S+/CS+ condition, whereas lever pressing under S/CS\udwas not altered. \udConclusions: The present study demonstrates\udthat the reinforcing effects of ethanol are markedly\udblunted by activation of the opioidergic N/OFQ receptor\udsystem. Moreover, the data provide evidence of the\udefficacy of N/OFQ to prevent reinstatement of ethanolseeking\udbehaviour elicited by environmental conditioned stimuli.