Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice
Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice
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DOI：
10.1038/bjp.2008.96
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发表时间：
2008-05-01
影响因子：
7.3
通讯作者：
Calo, G.
中科院分区：
文献类型：
--
作者：
Rizzi, A.;Vergura, R.;Calo, G.
背景与目的：神经肽S(NPS)是近年来发现的一种孤儿受体的内源性配体，现被称为NPS受体。在体内，NPS通过增加觉醒和施加类似焦虑的效果来产生独特的行为特征。在本研究中，我们进一步评估了NPS在体内对小鼠的影响。实验方法：侧脑室注射NPS对瑞士小鼠的运动活动(LA)、翻正反射(RR)恢复和焦虑状态(用高架迷宫(EPM)和应激性高温(SIH)测试)的影响进行评估。关键结果：NPS(0.01-1nmoL/只)显著增加幼鼠、习惯于测试笼子的小鼠和安定镇静动物(5 mg kg(-1))的LA。在RR试验中，NPS剂量依赖地减少了安定(15 mg kg(-1))引起的RR丧失的动物比例和它们的睡眠时间。在EPM和SIH测试中，NPS分别通过增加动物张开双臂的时间和降低SIH反应来剂量依赖性地诱发类似焦虑的效应。结论和启示：我们提供了进一步的证据，证明NPS作为一种新的唤醒和焦虑相关行为的调节器，通过促进一种独特的效应模式：刺激与焦虑相关。因此，NPS受体配体可能代表着治疗睡眠和焦虑症的创新药物。
Background and purpose: Neuropeptide S (NPS) was recently identified as the endogenous ligand of an orphan receptor, now referred to as the NPS receptor. In vivo, NPS produces a unique behavioural profile by increasing wakefulness and exerting anxiolytic-like effects. In the present study, we further evaluated the effects of in vivo supraspinal NPS in mice.Experimental approach: Effects of NPS, injected intracerebroventricularly (i.c.v.), on locomotor activity (LA), righting reflex (RR) recovery and on anxiety states (measured with the elevated plus maze (EPM) and stress-induced hyperthermia (SIH) tests) were assessed in Swiss mice.Key results: NPS (0.01-1 nmol per mouse) caused a significant increase in LA in naive mice, in mice habituated to the test cages and in animals sedated with diazepam (5 mg kg(-1)). In the RR assay, NPS dose dependently reduced the proportion of animals losing the RR in response to diazepam (15 mg kg(-1)) and their sleeping time. In the EPM and SIH test, NPS dose dependently evoked anxiolytic-like effects by increasing the time spent by animals in the open arms and reducing the SIH response, respectively.Conclusions and implications: We provide further evidence that NPS acts as a novel modulator of arousal and anxiety-related behaviours by promoting a unique pattern of effects: stimulation associated with anxiolysis. Therefore, NPS receptor ligands may represent innovative drugs for the treatment of sleep and anxiety disorders.