Attenuation of ethanol self-administration and of conditioned reinstatement of alcohol-seeking behaviour by the antiopioid peptide nociceptin/orphanin FQ in alcohol-preferring rats
Attenuation of ethanol self-administration and of conditioned reinstatement of alcohol-seeking behaviour by the antiopioid peptide nociceptin/orphanin FQ in alcohol-preferring rats
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DOI：
10.1007/s00213-003-1645-1
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发表时间：
2004-03-01
影响因子：
3.4
通讯作者：
Massi, M
中科院分区：
文献类型：
--
作者：
Ciccocioppo, R;Economidou, D;Massi, M
理由。阿片样孤儿受体NOP的内源性配体孤啡肽/孤啡肽FQ（N/OFQ）被证明可以减少家庭笼乙醇消耗，乙醇诱导的条件性位置偏好和应激诱导的酒精寻求行为的恢复。目标.本研究，使用遗传选择的Marchigian撒丁岛酒精偏好（msP）大鼠，旨在评估这种阿片肽对10%乙醇和10%蔗糖自我管理的影响，根据固定比例1（FR 1）或渐进比例（PR）的强化计划。此外，使用复发的实验模型，其中大鼠被训练为在存在橙子气味（S+）和1-s提示光（CS+）的辨别刺激的情况下杠杆按压乙醇或在存在茴香气味（S-）和1-s白色噪声（CS-）的情况下杠杆按压水，研究了N/oFQ对线索诱导的熄灭的乙醇反应的恢复的影响。结果亚慢性（6天）脑室内（i. c. v.）每只大鼠注射0.5 μ g或1.0 μ g N/OFQ显著减少了FR 1和PR强化方案下的酒精自我给药。相反，每只大鼠i. c. v.给药0.5、1.0或4.0 μ g肽不影响蔗糖自我给药。此外，i. c. v. N/OFQ（1.0-2.0杯每只大鼠）显着抑制恢复熄灭乙醇响应下的S+/CS+条件下，而杠杆按下S-/CS-没有改变。结论.本研究表明，乙醇的增强作用显着钝化阿片类药物能N/OFQ受体系统的激活。此外，这些数据提供了证据的功效N/OFQ，以防止恢复乙醇寻求行为引起的环境条件刺激。
Rationale. Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid-like orphan receptor NOP, was shown to reduce home-cage ethanol consumption, ethanol-induced conditioned place preference and stress-induced reinstatement of alcohol-seeking behaviour. Objectives. The present study, using genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, was designed to evaluate the effect of this opioid peptide on 10% ethanol and 10% sucrose self-administration, under a fixed-ratio 1 (FR 1) or a progressive-ratio (PR) schedule of reinforcement. Furthermore, using an experimental model of relapse in which rats were trained to lever press for ethanol in the presence of the discriminative stimulus of an orange odour (S+) and a 1-s cue light (CS+) or for water in the presence of anise odour (S-) and 1-s white noise (CS-), the effect of N/oFQ on cue-induced reinstatement of extinguished ethanol responding was investigated. Results. Sub-chronic (6 days) intracerebroventricular (i.c.v.) injection of 0.5 mug or 1.0 mug 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 mug of the peptide per rat did not affect sucrose self-administration. In addition, i.c.v. N/OFQ (1.0-2.0 mug per rat) significantly inhibited the reinstatement of extinguished ethanol responding under an S+/CS+ condition, whereas lever pressing under S-/CS- was not altered. Conclusions. The present study demonstrates that the reinforcing effects of ethanol are markedly blunted by activation of the opioidergic N/OFQ receptor system. Moreover, the data provide evidence of the efficacy of N/OFQ to prevent reinstatement of ethanol-seeking behaviour elicited by environmental conditioned stimuli.