論著
神經類固醇在阿普唑侖抗大鼠焦慮樣行為效應中的作用研究
梁鈺華 黎少英 陳淑華
【摘要】 【摘要】目的 在本研究中，我們通過行為學實驗檢測阿普唑侖抗大鼠的焦慮行為與部分腦區（如海馬體和前額皮層）中神經類固醇（如四氫孕酮，孕酮和孕烯醇酮）水平的聯系。方法 在本研究中，我們采用動物為SD大鼠，應用阿普唑侖對大鼠進行腹腔給藥（劑量為0.5，1，2 mg/kg）。給藥7日以后，每只大鼠分別通過一系列行為學實驗進行研究，如在第8日進行大鼠Vogel飲水沖突實驗，在第10日進行高架十字迷宮實驗，在第12日進行開場實驗。研究過程中，相關實驗的檢測指標如下：
【關鍵字】 阿普唑侖,焦慮癥,行為學,四氫孕酮,孕酮,孕烯醇酮
中圖分類號：文獻標識碼：文章編號：
[Abstract] 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 entering arms and the total time of entering arms. In the opening experiment, the number of fecal pellets, the number of crossings and rears were not affected by alprazolam treatment. In the aspect of mechanism research, the levels of progesterone and allopregnanolone in hippocampus and prefrontal cortex of rats increased significantly in the dose range of alprazolam (1 and 2 mg / kg), while the levels of pregnenolone did not change significantly. Conclusion The antianxiety effects of alprazolam in rats were related to the increase of allopregnanolone and progesterone levels in hippocampus and prefrontal cortex.
焦慮癥是一種社會性精神性障礙疾病。其發病影響著發病者的日常行為，目前，該疾病已成為全球關注和研究的精神性衛生難題。流行病學分析顯示全球患者中約有20%的患者可能終身性患有焦慮癥。焦慮癥患者主要有以下癥狀，如神經失常和不安，機體方面可能有自主性肌肉緊張等。其發病給國家，家庭和個人都帶來極大的負面影響[1-2]。據此，焦慮癥的研究和治療收到越來越多學者的關注。
目前尚未明確焦慮癥的發病機制，研究顯示焦慮癥的發病涉及多種因素。其中傳統研究的影響因素為腦區單胺功能和水平的紊亂。而在單胺遞質系統中，去甲腎上腺素，多巴胺，5-羥色胺（serotonin，5-HT）等遞質水平的異常是焦慮的發病機制重要影響因素[3]。根據焦慮癥的發病機制，5-HT再攝取抑制劑是臨床上常用的抗焦慮藥物之一，具體代表藥有舍曲林和帕羅西汀等[4]。該類藥物的作用機制是通過作用于機體中5-HT受體，使5-HT水平正?；a生抗焦慮作用。然而，5-HT再攝取抑制劑在臨床上抗焦慮須慎用，這體現在其具有起效較慢，有效率不高，可導致服用者自殺傾向等毒副作用[5]。根據以上該類藥物在臨床使用中的種種不足，挖掘強效低毒的抗焦慮藥物對臨床防治焦慮癥具有重要意義。
研究顯示神經類固醇與焦慮癥的發病有關，其體現在焦慮癥患者中，部分腦區（如前額平層和海馬體）的神經類固醇（如四氫孕酮，孕酮和孕烯醇酮等）水平的紊亂可能導致焦慮癥的發生[6]。而神經類固醇水平的正?；哂酗@著的抗精神性疾病的作用，如抗驚恐，抗應激，抗抑郁，抗焦慮等。其作用靶點是γ-氨基丁酸（γ-aminobutyric acid，GABA）受體。阿普唑侖是傳統的抗焦慮藥物，其起效途徑是作用于GABAA受體，提高GABA能中神經傳遞和突觸后抑制作用，使腦區多巴胺的釋放降低。然而，阿普唑侖的作用途徑是否與神經類固醇有聯系還在研究。而本研究也嘗試通過動物行為學實驗，評價神經類固醇（如四氫孕酮，孕酮和孕烯醇酮）在阿普唑侖抗焦慮效應中所扮演的角色。