Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
Faculty of Medicine, Institute of Physiology, Comenius University in Bratislava, Bratislava, Slovakia.
J Neurosci Res. 2018 Nov;96(11):1786-1797. doi: 10.1002/jnr.24280. Epub 2018 Aug 24.
Clozapine (CLZ) stimulates several brain areas some of them being sensitive to stress. Aim of the present study was to reveal whether 7-day CLZ administration may: (1) activate the selected forebrain areas; (2) modulate response of these structures to a single forced swimming episode (FSW); (3) modulate response of these structures to FSW after 13-day preconditioning with mild unpredictable stress complex (CMS). Used groups of male Wistar rats: (a) vehicle or CLZ treated for 7 days; (b) vehicle or CLZ treated for 7 days and on the 7th day exposed to FSW; (c) CMS exposed for 13 days, from the 8th day injected with vehicle or CLZ and on the 14th day exposed to FSW. Vehicle or CLZ (10 mg kg day in 0.1% acetic acid) were administered intraperitoneally. c-Fos quantification was performed 90 min after FSW in the medial prefrontal cortex (mPFC), dorsolateral (dLS) and ventrolateral (vLS) septum, dorsolateral (DLStr) and dorsomedial (DMStr) striatum, nucleus accumbens shell (NAc shell) and core (NAc core), and hypothalamic paraventricular nucleus (PVN). In unstressed animals CLZ increased c-Fos expression in the mPFC, vLS, and PVN. After a single FSW, CLZ decreased the number of c-Fos immunoreactive cells in the vLS, DMStr, NAc shell, and NAc core. In CMS rats, CLZ suppressed c-Fos immunoreactivity in response to FSW in the PVN. Our data indicate that CLZ elicits different impact on neuronal activities in the brain areas studied and modifies the response of these structures to stress. CLZ effect seems to be affected by stress duration.
氯氮平（CLZ）刺激大脑的几个区域，其中一些区域对压力敏感。本研究的目的是揭示 7 天 CLZ 给药是否可能：（1）激活选定的前脑区域；（2）调节这些结构对单次强迫游泳（FSW）的反应；（3）调节这些结构对 13 天轻度不可预测应激复合（CMS）预处理后 FSW 的反应。使用的雄性 Wistar 大鼠组：（a）载体或 CLZ 处理 7 天；（b）载体或 CLZ 处理 7 天，第 7 天暴露于 FSW；（c）CMS 暴露 13 天，从第 8 天注射载体或 CLZ，第 14 天暴露于 FSW。载体或 CLZ（0.1%乙酸中的 10mgkg-1 天）腹膜内给药。在强迫游泳后 90 分钟，在中前额皮质（mPFC）、背外侧（dLS）和腹外侧（vLS）隔室、背外侧（DLStr）和背内侧（DMStr）纹状体、伏隔核壳（NAc 壳）和核心（NAc 核心）以及下丘脑室旁核（PVN）中进行 c-Fos 定量。在未应激动物中，CLZ 增加了 mPFC、vLS 和 PVN 中的 c-Fos 表达。单次 FSW 后，CLZ 减少了 vLS、DMStr、NAc 壳和 NAc 核心中 c-Fos 免疫反应细胞的数量。在 CMS 大鼠中，CLZ 抑制了 PVN 对 FSW 的 c-Fos 免疫反应性。我们的数据表明，CLZ 对研究中大脑区域的神经元活动产生不同的影响，并调节这些结构对压力的反应。CLZ 的作用似乎受到应激持续时间的影响。
