Bantsiele Guy Bernard, Bentué-Ferrer Danièle, Amiot Noëlla, Allain Hervé, Bourin Michel, Reymann Jean-Michel
Laboratoire de Pharmacologie, Faculté de Médecine, Université de Rennes 1, CS34317, 35043 Rennes, France.
Fundam Clin Pharmacol. 2004 Dec;18(6):685-92. doi: 10.1111/j.1472-8206.2004.00295.x.
We used two validated psychopharmacological methods, the forced swimming test (FST 20 min and 5 min) and the elevated plus-maze (EPM), to quantify depression-like and anxiety-like behavior induced by transient global cerebral ischemia in the rat. We also validated use of these methods for the study of antidepressant (imipramine) and anti-anxiety drugs (diazepam). Twelve days after surgery to provoke transient global ischemia, spontaneous motor activity was 40% higher in ischemic rats than in sham-operated controls. Duration of immobility during the FST 20 min and 5 min was 28 and 30% shorter, respectively, than in controls. Treatment with imipramine (3 x 30 mg/kg i.p.) induced a significantly shorter duration of immobility during the FST 5 min, but with no difference between ischemia and control rats. The EPM demonstrated that ischemia did not induce any change in the six behavior parameters measured. Diazepam (1.5 mg/kg i.p.) induced significant anxiolytic effects which were similar in ischemic and sham-operated animals. Both tests failed to demonstrate perturbed performance but conversely, these findings did disclose the sensitivity of ischemia-exposed rats to the action of imipramine and diazepam, demonstrating the usefulness of these tests as psychopharmocological tools for evaluating the effect of psychotropics in the ischemic rat.
我们采用了两种经过验证的精神药理学方法,即强迫游泳试验(FST,20分钟和5分钟)和高架十字迷宫试验(EPM),来量化大鼠短暂性全脑缺血诱导的抑郁样和焦虑样行为。我们还验证了这些方法在抗抑郁药(丙咪嗪)和抗焦虑药(地西泮)研究中的应用。在诱发短暂性全脑缺血的手术后12天,缺血大鼠的自发运动活性比假手术对照组高40%。在FST的20分钟和5分钟期间,不动时间分别比对照组短28%和30%。丙咪嗪(3×30mg/kg腹腔注射)治疗在FST的5分钟期间使不动时间显著缩短,但缺血大鼠和对照大鼠之间无差异。EPM试验表明,缺血并未引起所测六个行为参数的任何变化。地西泮(1.5mg/kg腹腔注射)诱导了显著的抗焦虑作用,在缺血动物和假手术动物中相似。两项试验均未显示行为表现受干扰,但相反,这些发现确实揭示了缺血大鼠对丙咪嗪和地西泮作用的敏感性,证明了这些试验作为精神药理学工具在评估精神药物对缺血大鼠作用方面的有用性。