东莨菪碱对大鼠强迫游泳行为的影响及其作用靶点

目的 阐明东莨菪碱发挥抗抑郁作用的可能脑区和靶点。方法 明确东莨菪碱的抗抑郁样作用：将正常Sprague Dawley （SD）大鼠采用数字表法随机分为东莨菪碱组和0.9%（质量分数）氯化钠注射液对照组，腹腔注射25 μg/kg东莨菪碱或等体积0.9%（质量分数）氯化钠注射液，24 h后进行旷场实验和强迫游泳实验以评价东莨菪碱对大鼠抑郁样行为的影响；明确东莨菪碱发挥抗抑郁效应的脑区：在腹腔注射25 μg/kg东莨菪碱前1 h向大鼠内侧前额叶皮质（medial prefrontal cortex，mPFC）立体定位注射γ-氨基丁酸-A （γ-aminobutyric acid-A，GABA-A）受体激动剂蝇蕈醇（Muscimol）1.25 μg，24 h后观察东莨菪碱的行为学效应是否被阻断；探索东莨菪碱抗抑郁的作用靶点：通过微量给药系统分批次分别向大鼠侧脑室注射毒蕈碱型乙酰胆碱受体2（muscarinic acetylcholine receptor 2，M₂）选择性拮抗剂（methoctramine，MCT）0.5、1和2 μg，对照组均给予2 μL 0.9%（质量分数）氯化钠注射液，24 h后利用旷场实验和强迫游泳测试评价大鼠行为学变化。结果 腹腔注射东莨菪碱24 h后，大鼠强迫游泳不动时间低于对照组（P<0.05），旷场总路程差异无统计学意义（P>0.05）；向mPFC注射Muscimol可明显增加东莨菪碱组大鼠的不动时间（P<0.01），旷场总路程差异无统计学意义（P>0.05）；与侧脑室注射0.9%（质量分数）氯化钠注射液相比，0.5 μg MCT不影响大鼠在强迫游泳实验中不动时间（P>0.05），1 μg MCT可明显降低影响大鼠不动时间（P<0.01），而2 μg MCT则可明显增加影响大鼠不动时间（P<0.05）。结论 东莨菪碱可能通过阻断mPFC的M₂受体发挥抗抑郁作用。

Effects of scopolamine on forced swimming behavior in rats and its possible action target

Objective To clarify the possible brain regions and targets to mediate antidepressant-like effects of scopolamine. Methods Sprague Dawley (SD) rats were randomly divided into scopolamine group and saline control group. The rats were intraperitoneally injected with scopolamine or equal volume saline. After 24 hours, open field test and forced swimming test were carried out to evaluate the effect of scopolamine on the behavior of rats. γ-Aminobutyric acid-A (GABA-A) receptor agonist Muscimol (1.25 μg)was stereotaxically injected into the medial prefrontal cortex (mPFC) of rats one hour before intraperitoneal injection of 25 μg/kg scopolamine. Behavioral effects were examined after 24 hours. 0.5 μg, 1 μg and 2 μg muscarinic acetylcholine receptor 2 (M₂) receptor selective antagonist methoctramine (MCT) were respectively injected into the lateral ventricle of rats by the micro dosing system, while the control group was given 2 μL saline. Behavioral effects were examined after 24 hours. Results After 24 hours of intraperitoneal injection of scopolamine, the immobility time in rats was lower than that in the control group (P<0.05), while no statistical difference was observed in the total distance of the open field (P>0.05). In Muscimol+scopolamine group, the immobility time in rats was significantly higher than that in scopolamine group (P<0.01). No statistical difference was observed in the total distance in the open field test (P>0.05). Compared with lateral ventricle injection of saline, 0.5 μg MCT had no effect on the immobility time (P>0.05), 1 μg MCT could significantly reduce the immobility time (P<0.01), whereas 2 μg MCT could significantly increase the immobility time (P<0.05). Conclusion Scopolamine may exert antidepressant-like effects by blocking the M₂ receptor of mPFC.