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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视上核血管加压素和催产素神经元 c-Fos 表达的影响。

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

机构信息

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic.

出版信息

Endocr Regul. 2020 Apr 1;54(2):77-84. doi: 10.2478/enr-2020-0010.

Abstract

OBJECTIVE

The goal of this study was to reveal the impact of four types of atypical antipsychotics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI), with different receptor-affinity profile and dissociation constant, on the activity of hypothalamic supraoptic nucleus (SON) vasopressinergic and oxytocinergic neurons.

METHODS

Male Sprague Dawley rats received a single injection of vehicle (VEH) (0.1 ml/100g), AMI (20 mg/kg), OLA (5 mg/kg), QUE (15 mg/kg/) or ARI (10 mg/kg). Ninety min after treatment, the animals were fixed by transcardial perfusion, the brains removed, and cryocut into serial coronal sections of 35 µm thickness. The sections were processed for c-Fos staining using an avidin-biotin-peroxidase complex and visualized by nickel intensified diaminobenzidine to reach black end product. Afterwards, the sections were exposed to vasopressin (AVP) and oxytocin (OXY) antibodies and the reaction product visualized by biotin-labeled fluorescent Alexa Fluor 568 dye. The data were evaluated from c-Fos and AVP or OXY merged sections.

RESULTS

The present study shows that all four antipsychotics applied induced c-Fos expression in the SON. With respect to the stimulation efficacy of the individual antipsychotics, estimated based on the quantity of c-Fos-labeled AVP and OXY neurons, could be a preferential action assigned to QUE over moderate effect of ARI and lower effect to OLA and reduced effect of AMI (VEH < AMI < OLA < ARI < QUE).

CONCLUSION

The present data for the first time provide an insight into the quantitative pattern of brain activity within the clusters of SON AVP and OXY cells in response to different atypical antipsychotics single treatment.

摘要

目的

本研究旨在揭示四种不同受体亲和力和离解常数的非典型抗精神病药(氨磺必利(AMI)、奥氮平(OLA)、喹硫平(QUE)和阿立哌唑(ARI))对下丘脑视上核(SON)血管加压素能和催产素能神经元活性的影响。

方法

雄性 Sprague Dawley 大鼠接受单次注射 vehicle(VEH)(0.1ml/100g)、AMI(20mg/kg)、OLA(5mg/kg)、QUE(15mg/kg)或 ARI(10mg/kg)。治疗 90min 后,通过心脏灌注固定动物,取出大脑,并用 35µm 厚的连续冠状切片进行冷冻切片。使用亲和素-生物素-过氧化物酶复合物对切片进行 c-Fos 染色,并用镍强化二氨基联苯胺可视化,以达到黑色终产物。然后,将切片暴露于血管加压素(AVP)和催产素(OXY)抗体中,并用生物素标记的荧光 Alexa Fluor 568 染料可视化反应产物。从 c-Fos 和 AVP 或 OXY 合并切片中评估数据。

结果

本研究表明,所有四种抗精神病药均在 SON 中诱导 c-Fos 表达。就个体抗精神病药的刺激效果而言,基于 c-Fos 标记的 AVP 和 OXY 神经元的数量进行估计,可以优先分配给 QUE,其次是 ARI 中等效果,OLA 效果较低,AMI 效果降低(VEH<AMI<OLA<ARI<QUE)。

结论

本研究首次提供了关于不同非典型抗精神病药单次治疗对 SON 中 AVP 和 OXY 细胞簇脑活动的定量模式的见解。

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