Department of Pharmaceutical Sciences, University of California Irvine, 360 Med Surge 2, Irvine, CA 92697-4625, USA.
Behav Brain Res. 2009 Dec 14;205(1):1-9. doi: 10.1016/j.bbr.2009.07.024. Epub 2009 Jul 29.
Central administration of neuropeptide S (NPS) in rodents induces arousal and prolonged wakefulness as well as anxiolytic-like effects. NPS has also been implicated in modulation of cognitive functions and energy homeostasis. Here we present a comprehensive phenotypical analysis of mice carrying a targeted mutation in the NPS receptor (NPSR) gene. NPSR knockout mice were found to exhibit reduced exploratory activity when challenged with a novel environment, which might indicate attenuated arousal. We also observed attenuated late peak wheel running activity in NPSR knockout mice, representing reduced activity during the subjective evening. These mice also displayed increased anxiety-like behaviors when compared to their wildtype littermates, although analysis of anxiety behaviors was limited by genetic background influences. Unexpectedly, NPSR knockout mice showed enhanced motor performance skills. No phenotypical differences were detected in the forced-swim test, startle habituation and pre-pulse inhibition paradigms. Together, these data indicate that the endogenous NPS system might be involved in setting or maintaining behavioral arousal thresholds and that the NPS system might have other yet undiscovered physiological functions.
在啮齿动物中，神经肽 S（NPS）的中枢给药会引起觉醒和长时间的清醒，以及类似抗焦虑的作用。NPS 还被牵涉到认知功能和能量稳态的调节中。在这里，我们介绍了一种针对 NPS 受体（NPSR）基因的靶向突变的小鼠的综合表型分析。NPSR 敲除小鼠在面对新环境时表现出较低的探索活动，这可能表明它们的觉醒程度降低。我们还观察到 NPSR 敲除小鼠的后期峰值轮跑活动减弱，这代表在主观晚上的活动减少。与野生型同窝仔相比，这些小鼠也表现出增加的焦虑样行为，尽管焦虑行为的分析受到遗传背景的影响。出乎意料的是，NPSR 敲除小鼠显示出增强的运动表现技能。在强迫游泳试验、惊跳习惯化和预脉冲抑制范式中未检测到表型差异。总之，这些数据表明内源性 NPS 系统可能参与设定或维持行为觉醒阈值，并且 NPS 系统可能具有其他尚未发现的生理功能。
