Institute for Pharmacology & Toxicology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Department of Systems Physiology of Learning, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Genes Brain Behav. 2020 Mar;19(3):e12621. doi: 10.1111/gbb.12621. Epub 2020 Jan 2.
Neuropeptide S (NPS) is a neuropeptide involved in the regulation of fear. Because safety learning is impaired in patients suffering from anxiety-related psychiatric disorders, and polymorphisms of the human neuropeptide S receptor (NPSR) gene have also been associated with anxiety disorders, we wanted to investigate whether NPSR-deficiency interferes with safety learning, and how prior stress would affect this type of learning. We first investigated the effect of pre-exposure to two different types of stressors (electric stimuli or immobilization) on safety learning in female and male C57Bl/6 mice, and found that while stress induced by electric stimuli enhanced safety learning in males, there were no differences in safety learning following immobilization stress. To further investigate the role of the NPS system in stress-induced modulation of safety learning, we exposed NPSR-deficient mice to stress induced by electric stimuli 10 days before safety learning. In nonstressed male mice, NPSR-deficiency enhanced safety learning. As in male C57Bl/6 mice, pre-exposure to electric stimuli increased safety learning in male NPSR +/+ mice. This pre-exposure effect was blocked in NPSR-deficient male mice showing impaired, but still intact, safety learning in comparison to their NPSR +/+ and NPSR +/- littermates. There was neither a pre-exposure nor a genotype effect in female mice. Our findings provide evidence that pre-exposure to stress induced by electric stimuli enhances safety learning in male mice, and that NPSR-deficiency prevents the beneficial effect of stress exposure on safety learning. We propose an inverted U-shape relationship between stress and safety learning.
神经肽 S（NPS）是一种参与恐惧调节的神经肽。由于患有焦虑相关精神障碍的患者的安全学习受损，并且人类神经肽 S 受体（NPSR）基因的多态性也与焦虑障碍有关，因此我们想研究 NPSR 缺乏是否会干扰安全学习，以及先前的压力如何影响这种类型的学习。我们首先研究了两种不同类型的应激源（电刺激或固定）预先暴露对雌性和雄性 C57Bl/6 小鼠安全学习的影响，发现电刺激引起的应激增强了雄性的安全学习，而固定应激后安全学习没有差异。为了进一步研究 NPS 系统在应激诱导的安全学习调节中的作用，我们在安全学习前 10 天用电刺激使 NPSR 缺陷型小鼠暴露于应激中。在未应激的雄性小鼠中，NPSR 缺陷增强了安全学习。与 C57Bl/6 雄性小鼠一样，电刺激预先暴露增加了雄性 NPSR +/+ 小鼠的安全学习。这种预先暴露的效果在 NPSR 缺陷型雄性小鼠中被阻断，与 NPSR +/+ 和 NPSR +/-同窝小鼠相比，其安全学习受损，但仍完整。雌性小鼠中既没有预先暴露也没有基因型效应。我们的研究结果表明，电刺激诱导的应激预先暴露增强了雄性小鼠的安全学习，而 NPSR 缺乏阻止了应激暴露对安全学习的有益影响。我们提出了应激与安全学习之间的倒 U 形关系。
