Merali Z, Cayer C, Kent P, Anisman H
Department of Psychology, University of Ottawa, Ottawa, ON, Canada.
Psychopharmacology (Berl). 2008 Nov;201(1):115-23. doi: 10.1007/s00213-008-1252-2. Epub 2008 Aug 1.
Nesfatin-1, derived from the protein NEFA/nucleobindin2 (NUCB2), is a newly identified peptide that acts as a potent satiety agent. It has been reported that peptides involved in the regulation of ingestive behavior are also involved in the regulation of the stress response. However, the relation between nesfatin-1 and stressor-related behaviors like anxiety and/or fear has not yet been investigated.
The effects of intracerebroventricular (ICV) injection of nesfatin-1 (0, 5, and 25 pmol/3 microl) were assessed in several paradigms that are thought to reflect anxiety and/or fear in rats.
Consistent with an anxiogenic effect, nesfatin-1 dose-dependently decreased the percentage of time spent on the open arms of the elevated plus maze, increased latency to approach, and decreased consumption of a palatable snack in an anxiogenic (unfamiliar) environment. Moreover, ICV nesfatin-1 increased the fear-potentiated startle response and the time spent freezing to both context and conditioned cues in a conditioned emotional response test.
These findings suggest that in addition to its role as a satiety peptide, nesfatin-1 may also be involved in the mediation of anxiety- and/or fear-related responses.
Nesfatin-1由蛋白质NEFA/核结合蛋白2(NUCB2)衍生而来,是一种新发现的肽,可作为一种有效的饱腹感因子。据报道,参与调节摄食行为的肽也参与应激反应的调节。然而,nesfatin-1与焦虑和/或恐惧等应激源相关行为之间的关系尚未得到研究。
在几种被认为能反映大鼠焦虑和/或恐惧的范式中,评估脑室内(ICV)注射nesfatin-1(0、5和25皮摩尔/3微升)的效果。
与致焦虑作用一致,nesfatin-1剂量依赖性地降低了高架十字迷宫开放臂上的停留时间百分比,增加了接近潜伏期,并减少了在致焦虑(陌生)环境中对美味小吃的摄入量。此外,在条件性情绪反应测试中,脑室内注射nesfatin-1增加了恐惧增强的惊吓反应以及对环境和条件线索冻结的时间。
这些发现表明,nesfatin-1除了作为饱腹感肽发挥作用外,还可能参与焦虑和/或恐惧相关反应的介导。