Zoicas Iulia, Menon Rohit, Neumann Inga D
Department of Behavioural and Molecular Neurobiology, University of Regensburg, Regensburg, Germany; Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
Department of Behavioural and Molecular Neurobiology, University of Regensburg, Regensburg, Germany.
Neuropharmacology. 2016 Sep;108:284-91. doi: 10.1016/j.neuropharm.2016.03.054. Epub 2016 Apr 1.
Neuropeptide S (NPS) has anxiolytic effects and facilitates extinction of cued fear in rodents. Here, we investigated whether NPS reverses social fear and social avoidance induced by social fear conditioning (SFC) and acute social defeat (SD), respectively, in male CD1 mice. Our results revealed that intracerebroventricular NPS (icv; 10 and 50 nmol/2 μl) reversed fear of unknown con-specifics induced by SFC and dose-dependently reduced avoidance of known aggressive con-specifics induced by SD. While 50 nmol of NPS completely reversed social avoidance and reinstated social preference, 10 nmol of NPS reduced social avoidance, but did not completely reinstate social preference in socially-defeated mice. Further, a lower dose (1 nmol/2 μl) of NPS facilitated the within-session extinction of cued fear, while a higher dose (10 nmol/2 μl) reduced the expression of cued fear. We could also confirm the anxiolytic effects of NPS (1, 10 and 50 nmol/2 μl) on the elevated plus-maze (EPM), which were not accompanied by alterations in locomotor activity either on the EPM or in the home cage. Finally, we could show that icv infusion of the NPS receptor 1 antagonist D-Cys((t)Bu)(5)-NPS (10 nmol/2 μl) did not alter SFC-induced social fear, general anxiety and locomotor activity. Taken together, our study extends the potent anxiolytic profile of NPS to a social context by demonstrating the reduction of social fear and social avoidance, thus providing the framework for studies investigating the involvement of the NPS system in the regulation of different types of social behaviour.
神经肽 S（NPS）具有抗焦虑作用，并有助于消除啮齿动物的线索性恐惧。在此，我们研究了 NPS 是否能分别逆转雄性 CD1 小鼠中由社会恐惧条件反射（SFC）和急性社会挫败（SD）诱导的社会恐惧和社会回避。我们的结果显示，脑室内注射 NPS（icv；10 和 50 nmol/2 μl）可逆转 SFC 诱导的对陌生同种个体的恐惧，并剂量依赖性地减少 SD 诱导的对已知攻击性同种个体的回避。虽然 50 nmol 的 NPS 完全逆转了社会回避并恢复了社会偏好，但 10 nmol 的 NPS 减少了社会回避，但并未完全恢复社会挫败小鼠的社会偏好。此外，较低剂量（1 nmol/2 μl）的 NPS 促进了线索性恐惧在实验过程中的消退，而较高剂量（10 nmol/2 μl）则降低了线索性恐惧的表达。我们还可以证实 NPS（分别为 1、10 和 50 nmol/2 μl）对高架十字迷宫（EPM）具有抗焦虑作用，且这并未伴随着 EPM 或家笼中运动活动的改变。最后，我们可以表明，脑室内注射 NPS 受体 1 拮抗剂 D-Cys((t)Bu)(5)-NPS（10 nmol/2 μl）不会改变 SFC 诱导的社会恐惧、一般焦虑和运动活动。综上所述，我们的研究通过证明社会恐惧和社会回避的减少，将 NPS 强大的抗焦虑作用扩展到了社会情境中，从而为研究 NPS 系统在不同类型社会行为调节中的作用提供了框架。
