神经类固醇在阿普唑仑抗大鼠焦虑样行为效应中的作用研究  

The Role of Neurosteroids in the Brain in the Anxiolytic-like Effects of Alprazolam in Rats

作　　者：梁钰华 黎少英 陈淑华 LIANG Yu-hua;LI Shao-ying;CHEN Shu-hua(Guangzhou Panyu Central hospital,Guangzhou 511400)

机构地区：[1]广州市番禺中心医院,广东广州511400

出　　处：《中国医药指南》2020年第19期7-9,12,共4页Guide of China Medicine

摘　　要：目的在本研究中,我们通过行为学实验检测阿普唑仑抗大鼠的焦虑行为与部分脑区(如海马体和前额皮层)中神经类固醇(如四氢孕酮,孕酮和孕烯醇酮)水平的联系。方法在本研究中,我们采用动物为SD大鼠,应用阿普唑仑对大鼠进行腹腔给药(剂量为0.5、1、2 mg/kg)。给药7 d以后,每只大鼠分别通过一系列行为学实验进行研究,如在第8日进行大鼠Vogel饮水冲突实验,在第10日进行高架十字迷宫实验,在第12日进行开场实验。研究过程中,相关实验的检测指标如下:在大鼠Vogel饮水冲突实验中检测大鼠在3 min中的舔水次数;在高架十字迷宫实验中,分别检测5 min内大鼠总入臂次数,时间和开臂进入次数和停留时间;在开场实验中,分别检测5 min内大鼠的粪便颗粒数,跨格数,站立次数。在所有行为学实验完成以后,我们在组织学层面进一步探讨阿普唑仑抗焦虑行为的作用机制。我们提取与焦虑发病相关的脑区(如海马体和前额皮层)。然后,实验采用酶联免疫吸附剂测定法(Enzyme-Linked ImmunoSorbent Assay,ELISA)分别评价以上脑区中神经类固醇水平(如四氢孕酮,孕酮和孕烯醇酮)的改变。结果在大鼠Vogel饮水冲突实验中,大鼠舔水次数在阿普唑仑(1、2 mg/kg)处理后明显增加;在高架十字迷宫实验中,阿普唑仑(1、2 mg/kg)处理后,大鼠在十字迷宫的开臂进入次数和开臂停留时间明显提高。然而,总入臂次数和总入臂时间却没有明显的改变;在开场实验中,大鼠的粪便颗粒数,跨格数和站立次数均不受阿普唑仑处理影响。在机制研究方面,大鼠海马体和前额皮层中的孕酮和四氢孕酮水平在阿普唑仑(1和2 mg/kg)的剂量范围下显著提高,而孕烯醇酮的水平则无显著性改变。结论剂量下阿普唑仑在大鼠中抗焦虑行为与提高海马体和前额皮层中四氢孕酮和孕酮的水平相关。Objective In the present study,we examined the association of anxiety behavior of apazolam-resistant rats with levels of neurosteroids(e.g.,allopregnanolone,progesterone,and progesterone)in some brain regions(e.g.,hippocampus and prefrontal cortex)through behavioral experiments.Methods In this study,we used SD rats as animals,and applied alprazolam to rats for intraperitoneal administration(dose of 0.5,1,2 mg/kg).After 7 days of administration,each rat was studied through a series of behavioral experiments,such as Vogel drinking water conflict experiment on the 8th day,elevated cross maze experiment on the 10th day and opening experiment on the 12th day.In the research process,the detection indicators of relevant experiments are as follows:in the Vogel drinking water conflict experiment of rats,the number of licking in 3 min was detected;in the elevated cross maze experiment,the total number of times of entering the arm,the time of entering the arm,the number of times of entering the arm and the time of staying in the arm were detected respectively in 5 min;in the opening experiment,the number of fecal particles,the number of cross lattice and the number of standing were detected respectively in 5 min.After the completion of all behavioral experiments,we further explored the mechanism of alprazolam's anti anxiety behavior at the histological level.We extract brain regions(such as the hippocampus and prefrontal cortex)that are associated with anxiety.Then,enzyme-linked immunosorbent assay(ELISA)was used to evaluate the changes of the levels of neurosteroids(such as allopregnanolone,progesterone and pregnenolone)in the above brain regions.Results In the Vogel drinking water conflict experiment,the number of licking was significantly increased after alprazolam(1 and 2 mg/kg)treatment;in the elevated plus maze experiment,the number of arm opening entry and arm opening dwell time were significantly increased after alprazolam(1 and 2 mg/kg)treatment.However,there was no significant change in the total number of enterin

关 键 词：阿普唑仑 焦虑症 行为学 四氢孕酮 孕酮 孕烯醇酮 

分 类 号：R749.72[医药卫生—神经病学与精神病学]