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单剂量氨磺必利、奥氮平、喹硫平、阿立哌唑对大鼠下丘脑室旁核血管加压素和催产素神经元 c-Fos 表达的影响。

The effect of amisulpride, olanzapine, quetiapine, and aripiprazole single administration on c-Fos expression in vasopressinergic and oxytocinergic neurons of the rat hypothalamic paraventricular nucleus.

机构信息

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Dubravska Cesta 9, 84505 Bratislava, Slovakia.

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Dubravska Cesta 9, 84505 Bratislava, Slovakia.

出版信息

Neuropeptides. 2021 Jun;87:102148. doi: 10.1016/j.npep.2021.102148. Epub 2021 Apr 14.

Abstract

Antipsychotics, including amisulpride (AMI), quetiapine (QUE), aripiprazole (ARI), and olanzapine (OLA), are used to treat mental illnesses associated with psychotic symptoms. The effect of these drugs on c-Fos expression in vasopressinergic (AVP) and oxytocinergic (OXY) neurons was studied in the hypothalamic paraventricular nucleus (PVN) of rats. The presence of c-Fos in AVP and OXY perikarya was investigated in seven PVN cells segregations: the anterior (Ant), dorsal cup (Dc), wing-shaped (Wi), periventricular zone (Pe), circle-shaped core (Co) and shell of core (Sh), and the posterior (pPVN) after an acute treatment with AMI-20 mg/kg, QUE-15 mg/kg, ARI-10 mg/kg, and OLA-5 mg/kg/bw in rats. Ninety min after treatments, the animals were sacrificed by transcardial perfusion with fixative and the PVN area sliced into 35 μm thick coronal sections for immunohistochemistry. The c-Fos was processed by avidin-biotin-peroxidase complex intensified with nickel-enhanced 3,3'-diaminobenzidine tetrahydrochloride. Visualization of AVP- and OXY-synthesizing neurons was achieved by a fluorescent marker Alexa Flour 568. The c-Fos-AVP and c-Fos-OXY colocalizations were evaluated from c-Fos stained sections merged with AVP or OXY ones. AMI, QUE, ARI, and OLA, single administration distinctly increased the c-Fos expression in each of the PVN cells segregations. QUE induced the highest magnitude of activation of AVP and OXY neurons, while OLA and AMI had only moderate effects. Incontestable variabilities detected in c-Fos expression in PVN AVP and OXY neurons extend the knowledge of selected antipsychotics extra-striatal actions and may also be helpful in a presumption of their possible functional impact.

摘要

抗精神病药,包括氨磺必利(AMI)、喹硫平(QUE)、阿立哌唑(ARI)和奥氮平(OLA),用于治疗与精神病症状相关的精神疾病。本研究旨在研究这些药物对大鼠下丘脑室旁核(PVN)血管加压素能(AVP)和催产素能(OXY)神经元中 c-Fos 表达的影响。在急性给予 AMI-20mg/kg、QUE-15mg/kg、ARI-10mg/kg 和 OLA-5mg/kg/bw 后,通过免疫组织化学方法在 7 个 PVN 细胞分区(前(Ant)、背杯(Dc)、翼状(Wi)、室周带(Pe)、核心圆形区(Co)和核心壳区(Sh)和后(pPVN))中研究了 AVP 和 OXY 神经原中 c-Fos 的存在。治疗 90min 后,通过心脏灌流固定处死动物,并将 PVN 区域切成 35μm 厚的冠状切片进行免疫组织化学染色。c-Fos 通过avidin-biotin-peroxidase 复合物处理,并用镍增强的 3,3'-二氨基联苯胺四盐酸盐增强。通过荧光标记物 Alexa Flour 568 实现 AVP 和 OXY 合成神经元的可视化。通过将 c-Fos 染色的切片与 AVP 或 OXY 切片合并,评估 c-Fos-AVP 和 c-Fos-OXY 共定位。AMI、QUE、ARI 和 OLA 的单次给药明显增加了每个 PVN 细胞分区中的 c-Fos 表达。QUE 诱导 AVP 和 OXY 神经元的激活幅度最大,而 OLA 和 AMI 只有中等作用。在 PVN AVP 和 OXY 神经元中 c-Fos 表达的无可争议的可变性扩展了选定的抗精神病药的纹外作用的知识,也有助于推测其可能的功能影响。

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