Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice.
Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice.
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DOI：
10.1523/jneurosci.5256-08.2009
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发表时间：
2009-04-01
期刊：
影响因子：
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通讯作者：
Roberts AJ
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文献类型：
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作者：
Pañeda C;Huitron-Resendiz S;Frago LM;Chowen JA;Picetti R;de Lecea L;Roberts AJ
神经肽 S (NPS) 是一种最近发现的神经肽，可提高唤醒度和觉醒度，同时减少焦虑样行为。在这里，我们使用自我给药范例来证明，脑室内注射 NPS 可以以剂量依赖的方式恢复小鼠的已消失的可卡因寻求行为。在没有可卡因的情况下，最高剂量的 NPS (0.45 nM) 增加了主动杠杆压力，达到与自我给药期间观察到的水平相当的水平。此外，我们还研究了促肾上腺皮质激素释放因子受体 1 (CRF1) 在这种行为以及运动刺激和抗焦虑作用中的作用。 CRF1 敲除小鼠对 NPS 的运动兴奋剂或可卡因恢复作用均没有反应，但仍对其抗焦虑作用有反应。 CRF1拮抗剂antalarmin还可以阻断恢复模型中主动杠杆反应的增加以及NPS的运动激活特性，而不影响其抗焦虑作用。我们的研究结果表明，NPS 受体可能是药物滥用研究和治疗的重要靶点，并且 CRF1 介导 NPS 的可卡因寻求和运动刺激作用，但不介导其对焦虑样行为的影响。
Neuropeptide S (NPS) is a recently discovered neuropeptide that increases arousal and wakefulness while decreasing anxiety-like behavior. Here, we used a self-administration paradigm to demonstrate that intracerebroventricular infusion of NPS reinstates extinguished cocaine-seeking behavior in a dose-dependent manner in mice. The highest dose of NPS (0.45 nM) increased active lever pressing in the absence of cocaine to levels that were equivalent to those observed during self-administration. In addition, we examined the role of the corticotropin-releasing factor receptor 1 (CRF1) in this behavior as well as locomotor stimulation and anxiolysis. CRF1 knock-out mice did not respond to either the locomotor stimulant or cocaine reinstatement effects of NPS, but still responded to its anxiolytic effect. The CRF1 antagonist antalarmin also blocked the increase in active lever responding in the reinstatement model and the locomotor activating properties of NPS without affecting its anxiolytic actions. Our results suggest that NPS receptors may be an important target for drug abuse research and treatment and that CRF1 mediates the cocaine-seeking and locomotor stimulant effects of NPS, but not its effects on anxiety-like behavior.