阿普唑仑抗创伤后应激性障碍活性与脑内生理性变化相关性研究

The correlation between the physiological changes in the brain and the anti-PTSD-like effect of Alprazolam

目的探讨阿普唑仑抗创伤后应激性障碍（post—traumatic stress disorder,PTsD）行为活性与脑内四氢孕酮合成的相关性。方法建立单一长期应激（single—prolonged stress，SPS）模型，通过开场试验，强迫游泳试验和高架十字迷宫试验研究阿普唑仑抗PTSD的行为活性作用。在所有行为学试验后24h内，提取与PTSD相关的脑区，如前额皮层，海马体和杏仁核。酶联免疫吸附剂测定法（Enzyme—Linked Immuno Sorbent Assay，ELISA）检测其四氢孕酮含量。结果阿普唑仑（1和2mg／kg i．p）在强迫游泳试验中显著缩短SPS大鼠游泳不动时间[分别为（96．10±6．034）S和（93．40±12．38）s]和在高架十字迷宫中显著逆转SPS大鼠在开臂停留时间百分比（分别为23．80％±3．186％和30．00％±3．930％）与次数百分比的减少（分别为29．80％±2．909％和33．20％±3．527％），同时不影响实验动物的入臂总次数和总时间。在开场试验中，阿普唑仑不影响实验大鼠跨格数，直立次数和粪便颗粒数。此外，阿普唑仑可逆转SPS大鼠前额皮层[分别为（190．0±34．25）pg／mL和（206．7±16．87）pg／mL]，海马体[分别为（141．7±26．76）pg/mL和（175．8±25．70）pg／mL）和杏仁核[分别为（160．3±22.60）pg／mL和（191．7±24．55）pg／mL）四氢孕酮含量水平的下调。结论阿普唑仑不影响试验大鼠自发活动和具有显著的抗PTSD行为活性，该活性与上调前额皮层，海马体和杏仁核的四氢孕酮含量水平有关。

Objective To evaluate the role of allopregnanolone in the anti- post-traumatic stress disorder （PTSD）-like effect of Alprazolam. Methods The single-prolonged stress, SP model, was established. The anti-PTSD-like effect of Alprazolam was explored and evaluated through open field test, force swimming test, as well as elevated plus maze test. Also, allopregnanolone level in the prefrontal cortex, hippocampus and amydala was measured after all the behavioral tests by Enzyme-Linked ImmunoSorbent Assay （ELISA）. Results Alprazolam （1 and 2 mg/kg i.p）produced anti＇PTSD-like effect by decreasing immobility time in the forced swimming test （1 mg/kg i.p： 96.10±6.034 seconds and 2 mg/kg i.p： 93.40± 12.38 seconds, respectively）as well as by the percentage of the time spent in（ 1 mg/kg i.p： 23.80±3.186% and 2 mg/kg i.p： 30.00±3.930%, respectively）and the entries into（1 mg/kg i.p： 29.80±2.909% and 2 mg/kg i.p： 33.20±3.527%, respectively）the open arms in the elevated plus maze test, without affecting the total time and total entries in arms. In addition, Alprazolam did not affect the number of crossings, rears and fecal pellets in the open field test. Moreover, the alloprcgnanolone level in the prefrontal cortex（ 1 mg/kg i.p： 190.0±34.25 pg/mL and 2 mg/kg i.p： 206.7±16.87 pg/mL, respectively）, hippocampus （2 mg/kg i.p： 175.8±25.70 pg/mL）and amydala（ 1mg/kg i. p： 160.3 ± 22.60 pg/mL and 2 mg/kg i.p： 191.7 ±24.55 pg/mL, respectively）was increased with administration of Alprazolam. Conclusion These results indicate that Alprazolam exerts the anti-PTSD-like effects on behaviors that are associated with the stimulation of the allopregnanolone biosynthesis in brain.