Effects of the NOP agonist SCH221510 on producing and attenuating reinforcing effects as measured by drug self-administration in rats.
Effects of the NOP agonist SCH221510 on producing and attenuating reinforcing effects as measured by drug self-administration in rats.
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DOI：
10.1016/j.ejphar.2014.10.029
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发表时间：
2014-12-15
影响因子：
5
通讯作者：
Ko, Mei-Chuan
中科院分区：
文献类型：
--
作者：
Sukhtankar, Devki D.;Lagorio, Carla H.;Ko, Mei-Chuan
Nociceptin/Nociceptin FQ肽（NOP）受体激动剂减弱啮齿动物中吗啡诱导的条件性位置偏爱然而，目前尚不清楚NOP激动剂是否具有增强特性或是否可以抑制μ阿片受体（MOP）介导的增强，如通过啮齿动物中的药物自我给药所测量的。进一步了解NOP激动剂的行为效应可能表明它们在减弱阿片类药物的强化作用方面具有潜力。在研究的第一部分中，确定了选择性NOP激动剂SCH 221510的增强特性，并与全MOP激动剂瑞芬太尼在固定比例5（FR 5）和渐进比例（PR）药物自我给药方案下进行了比较。在第二部分中，测定了SCH 221510的全身和脑池内预处理的效果，并与MOP拮抗剂纳洛酮在减弱瑞芬太尼和非药物增强剂（蔗糖丸）的增强作用方面进行了比较。瑞芬太尼自我给药（0.3-10 μg/kg/输注）产生了双相剂量反应曲线，这是具有强化特性的药物的特征。SCH 221510（3-300 μg/kg/输注）自我给药导致PR下的剂量-反应曲线平坦且断点较早，表明药物缺乏强化价值。脑池内（但非全身）给予SCH 221510（0.3-3 μg）可减弱瑞芬太尼自我给药，与全身纳洛酮（0.03-0.3 mg/kg）相当。SCH 221510（1-3 μg）与纳洛酮（0.03-1 mg/kg）不同，减弱了对蔗糖颗粒的反应。SCH 221510的这两种作用可被NOP拮抗剂J-113397（0.3-3 μg）逆转。这些结果表明，SCH 221510在大鼠中不起麻醉剂的作用，并且它可以减弱MOP激动剂的增强值;因此，NOP激动剂用于治疗药物成瘾的潜在效用需要进一步评估。
Nociceptin/orphanin FQ peptide (NOP) receptor agonists attenuate morphine-induced conditioned place preference in rodents. However, it is not known whether NOP agonists have reinforcing properties or can inhibit mu opioid receptor (MOP)-mediated reinforcement as measured by drug self-administration in rodents. Further understanding the behavioral effects of NOP agonists could suggest them as having potential in attenuating reinforcing effects of opioids. In the first part of the study, reinforcing properties of selective NOP agonist SCH221510 were determined and compared with the full MOP agonist remifentanil under fixed-ratio 5 (FR5) and progressive-ratio (PR) schedules of drug self-administration. In the second part, effects of systemic and intracisternal pretreatment of SCH221510 were determined and compared with MOP antagonist naltrexone in attenuating reinforcing effects of remifentanil and a non-drug reinforcer (sucrose pellets). Remifentanil self-administration (0.3-10 μg/kg/infusion) generated a biphasic dose-response curve, characteristic of drugs with reinforcing properties. SCH221510 (3-300 μg/kg/infusion) self-administration resulted in flat dose-response curves and early break-points under the PR, indicative of drugs lacking reinforcing value. Intracisternally, but not systemically, administered SCH221510 (0.3-3 μg) attenuated remifentanil self-administration, comparable with systemic naltrexone (0.03-0.3 mg/kg). SCH221510 (1-3 μg), unlike naltrexone (0.03-1 mg/kg), attenuated responding for sucrose pellets. Both effects of SCH221510 were reversed by the NOP antagonist J-113397 (0.3-3 μg). These results suggest that SCH221510 does not function as a reinforcer in rats, and that it can attenuate the reinforcing value of MOP agonists; therefore, the potential utility of NOP agonists for the treatment of drug addiction warrants further evaluation.
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DOI：
10.1038/npp.2009.33
发表时间：
2009-08
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3
作者：
Di Giannuario, A;Pieretti, S
通讯作者：
Pieretti, S
DOI：
10.1124/jpet.108.139196
发表时间：
2008-09-01
影响因子：
3.5
作者：
Cooper, Ziva D.;Truong, Yen Nhu-Thi;Woods, James H.
通讯作者：
Woods, James H.
影响因子：
2.9
作者：
Baylon, GJ;Kaplan, HL;Sellers, EM
通讯作者：
Sellers, EM
DOI：
10.1073/pnas.090514397
发表时间：
2000-04-25
影响因子：
11.1
作者：
Jenck, F;Wichmann, J;Kilpatrick, G
通讯作者：
Kilpatrick, G