PE的抗焦虑作用研究

【作者】 王睿；

【导师】 陈思维；

【作者基本信息】 沈阳药科大学 ， 药理学， 2006， 硕士

【摘要】 本课题主要运用行为药理学手段研究了紫苏中某成份PE的抗焦虑作用及其对中枢神经系统的影响。研究结果显示：在小鼠高架十字迷路实验中，PE(150mg／kg，ig)显著增加小鼠在十字迷路中进入开臂次数的百分率并延长小鼠在开臂的滞留时间百分率；在小鼠明暗穿箱实验中，PE(150mg／kg，ig)在不影响活动性的情况下可使小鼠在明箱的停留时间显著延长；在小鼠孔板实验中，PE(150mg／kg，ig)可显著增加小鼠的探头次数和探头时间；在小鼠应激诱导的体温升高实验中，PE(150mg／kg，ig)可显著降低小鼠应激引起的体温升高；在小鼠隔离诱导攻击实验中，PE(150mg／kg，ig)可以显著降低隔离小鼠对入侵鼠的攻击时间；在小鼠对天敌防御反应实验中，PE(150mg／kg，ig)可以显著缩短小鼠对天敌的逃避距离，但对回避次数及平均逃跑速度的影响不显著；在追赶／逃跑实验中，PE各剂量组均可显著减少小鼠的反跑次数，PE(150～600mg／kg，ig)可减少小鼠调头次数；PE(150mg／kg，ig)可显著增加小鼠在直通道实验中的接近／撤退次数；在直通道强迫接触实验中，PE(75、150mg／kg，ig)可显著减少小鼠跳跃次数，PE(150mg／kg，ig)可显著减少小鼠直立次数；在关联防御实验中，PE(300mg／kg，ig)可显著减少小鼠的逃逸行为(跳跃、倚墙站立和爬墙)，PE各剂量组对小鼠越线次数的增加与预实验相比无显著性差异。PE各剂量对GABA_A受体拮抗剂印防己毒素(PTX)诱导的惊厥无拮抗作用，这提示其抗焦虑药效的发挥可能与GABA_A受体无关。在大鼠群居接触实验中，弱光不熟悉、强光不熟悉和强光熟悉环境下，PE(52.5mg／kg，ig)可以显著延长配对大鼠的主动接触时间；在大鼠孔板实验中，PE(52.5mg／kg，ig)可显著增加大鼠的探头次数并延长探头时间；在大鼠开场实验中，PE(26.25、52.5mg／kg，ig)可显著缩短大鼠进入开场中央区的潜伏期并增加进入次数；在条件化恐惧应激诱导大鼠僵滞行为实验中，PE(105mg／kg，ig)可显著减少大鼠累积僵滞行为的时间。PE(300mg／kg，ig)可延长戊巴比妥钠诱导小鼠的睡眠时间；PE(600mg／kg，ig)显著减少小鼠的自发活动；PE(75～300mg／kg，ig)不损伤小鼠在十字迷路上学习的获得和记忆能力；牵引实验和倾斜平板实验的结果显示，大剂量的PE(900mg／kg，ig)不损伤小鼠的肌肉协调能力。本研究结果显示PE具有显著的抗焦虑作用。更多还原

【Abstract】 The anxiolytic-like effects of PE in Perillae Herba were investigated by means of behavioral pharmacology for the first time. The other central-acting properties of PE were also examined to see whether clear differences could be observed between it and diazepam.In the elevated plus-maze test, after acute administration, PE (150mg/kg, ig) significantly increased the percentage of open arm entries and of time spent in open arms. In the light/dark transition test, PE (150mg/kg, ig) prolonged the time spent in light area without altering the locomotor activity of the animals. In the hole-board test, PE (150mg/kg, ig) caused increase in exploratory head-dipping in mice. In the test of stress-induced hyperthermia paradigm in singly-housed mice, PE (150mg/kg, ig) significantly inhibited stress-induced hyperthermia. In the isolation-induced aggression test, PE (150mg/kg, ig) reduced the total fighting time between isolation mouse and intruder mouse. In the mouse defense test battery, PE (150mg/kg, ig) significantly decreased avoidance distance without effect on the number of avoidance and mean flight speed; In the chase/flight test, PE decreased frequency of reversals at each dose, PE (150～600mg/kg, ig)significantly decreased frequency of orientations; In the straight alley test, PE (150mg/kg, ig) increased the number of approaches/withdrawals; In the forced contact test, PE (75、150mg/kg, ig) decreased the number of jumps significantly and PE (150mg/kg, ig) decreased frequency of upright postures; In the contextual test, PE (300mg/kg, ig) significantly decreased escape attempts (jump escapes, wall rears, wall climbs). PE increased the number of line crossings but without significant effects vs. pretest at each dose.PE and diazepam were differentiated in the GABA_A receptor antagonist picrotoxin-induced seizure assay, with diazepam antagonizing seizures while PE was inactive. This suggests that the anxiolytic-like effect of PE may be different from that of diazepam.In the social interaction test, PE (52.5mg/kg, ig) in the LU (low light, unfamiliar)、HU (high light, unfamiliar) and HF (high light, familiar) test conditions all significantly increased social interaction time of pairs of rats. PE (52.5mg/kg, ig) caused increase in exploratory head-dipping in the hole-board test of rats. In the open field test, PE (26.25～52.5mg/kg, ig) significantly increased the number of entries into the central arena, demonstrating the antithgmotactic effect. In the test of conditioned fear stress-induced freezing in rats, PE (105mg/kg, ig) reduced freezing time significantly. In general, the results above indicate that PE at specific doses, possesses anxiolytic properties in different anxiety models.PE (300mg/kg, ig) prolonged pentobarbital sodium-induced sleeping time and PE (600mg/kg, ig) decreased motor activity of mice in the spontaneous motor activity test, which showed that PE might inhibit the central system. At doses eliciting the anxiolytic effect, PE produced neither disrupting learning and memory, nor impairing muscle tone.In conclusion, these findings indicate that PE exhibits an anxiolytic-like effect at given dosage.更多还原