Pañeda Covadonga, Huitron-Resendiz Salvador, Frago Laura M, Chowen Julie A, Picetti Roberto, de Lecea Luis, Roberts Amanda J
Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, California 92037, USA.
J Neurosci. 2009 Apr 1;29(13):4155-61. doi: 10.1523/JNEUROSCI.5256-08.2009.
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 (CRF(1)) in this behavior as well as locomotor stimulation and anxiolysis. CRF(1) 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 CRF(1) 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 CRF(1) mediates the cocaine-seeking and locomotor stimulant effects of NPS, but not its effects on anxiety-like behavior.
神经肽S（NPS）是一种最近发现的神经肽，它能增强觉醒和清醒状态，同时减少类似焦虑的行为。在此，我们采用自我给药范式来证明，向小鼠脑室内注射NPS能以剂量依赖的方式恢复已消退的觅可卡因行为。NPS的最高剂量（0.45 nM）在无可卡因的情况下使主动压杆行为增加到与自我给药期间观察到的水平相当。此外，我们研究了促肾上腺皮质激素释放因子受体1（CRF(1)）在这种行为以及运动刺激和抗焦虑作用中的作用。CRF(1)基因敲除小鼠对NPS的运动刺激或可卡因复吸效应均无反应，但仍对其抗焦虑效应有反应。CRF(1)拮抗剂安他乐也能阻断复吸模型中主动压杆反应的增加以及NPS的运动激活特性，而不影响其抗焦虑作用。我们的结果表明，NPS受体可能是药物滥用研究和治疗的一个重要靶点，并且CRF(1)介导了NPS的觅可卡因和运动刺激效应，但不介导其对类似焦虑行为的影响。
