Antagonism of the neuropeptide S receptor with RTI-118 decreases cocaine self-administration and cocaine-seeking behavior in rats.
Antagonism of the neuropeptide S receptor with RTI-118 decreases cocaine self-administration and cocaine-seeking behavior in rats.
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DOI：
10.1016/j.pbb.2012.09.003
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发表时间：
2012-12
影响因子：
3.6
通讯作者：
Goeders, Nicholas E.
中科院分区：
文献类型：
--
作者：
Schmoutz, Christopher D.;Zhang, Yanan;Runyon, Scott P.;Goeders, Nicholas E.
神经肽S （NPS）是一种神经调节肽，通过g蛋白偶联受体调节睡眠、焦虑和行为唤醒。最近的研究发现，脑室内NPS可以增加啮齿动物的可卡因和酒精自我给药，这表明在奖励相关的神经回路中起关键作用。据推测，NPS系统的拮抗作用可能是可卡因滥用药物治疗的一种新策略。为此，开发了一种小分子NPSR拮抗剂（RTI-118），并在可卡因寻求和可卡因服用的动物模型中进行了测试。雄性Wistar大鼠（n=54）被训练在FR4交替计划下自我服用可卡因和食物，当给予RTI-118时，可卡因摄入量表现出特定的剂量依赖性减少。RTI-118还减少了条件提示、育亨宾和启动剂量可卡因诱导的已消失的可卡因寻求行为的恢复。这些数据支持神经肽S受体的拮抗作用可能最终显示出减少可卡因使用和复发的功效。
Neuropeptide S (NPS) is a neuromodulatory peptide, acting via a G-protein-coupled receptor to regulate sleep, anxiety and behavioral arousal. Recent research has found that intracerebroventricular NPS can increase cocaine and alcohol self-administration in rodents, suggesting a key role in reward-related neurocircuitry. It is hypothesized that antagonism of the NPS system might represent a novel strategy for the pharmacological treatment of cocaine abuse. To this end, a small-molecule NPSR antagonist (RTI-118) was developed and tested in animal models of cocaine seeking and cocaine taking. Male Wistar rats (n=54) trained to self-administer cocaine and food under a concurrent alternating FR4 schedule exhibited specific dose-dependent decreases in cocaine intake when administered RTI-118. RTI-118 also decreased the reinstatement of extinguished cocaine-seeking behavior induced by conditioned cues, yohimbine and a priming dose of cocaine. These data support the hypothesis that antagonism of the neuropeptide S receptor may ultimately show efficacy in reducing cocaine use and relapse.
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