Kulkarni S K, Dhir Ashish
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
Prog Neuropsychopharmacol Biol Psychiatry. 2007 Aug 15;31(6):1248-54. doi: 10.1016/j.pnpbp.2007.05.002. Epub 2007 May 18.
The forced swim test (FST) and tail suspension test (TST) are widely used as animal models for screening potential antidepressants. Immobility or despair behavior produced in both FST and TST are taken as paradigm of depression and antidepressant drugs reduce the immobility period. Recent studies have suggested dissimilar hemodynamic, behavioral, physiological and pharmacological variations in these two models. Also, studies have proposed the significance of strain in these models of despair in an attempt to replicate results from one laboratory to another. The present study was undertaken to compare the antidepressant action of four major classes of antidepressants namely tricyclics (imipramine), selective serotonin reuptake inhibitor (fluoxetine), dual reuptake inhibitor of serotonin and norepinephrine (venlafaxine) and atypical antidepressants (mianserin and trazodone) using male laca mice in order to validate the two test procedures. Total immobility period was recorded during the period of 6 min in both the tests and the results were expressed as percentage decrease in immobility period with respect to vehicle control. Chlorpromazine (4 mg/kg, i.p.) or pentobarbitone (20 mg/kg, i.p.) were used as negative control. Imipramine (2, 5, 10 and 20 mg/kg), fluoxetine (5, 10, 20 and 40 mg/kg), or venlafaxine (2, 4, 8 and 16 mg/kg) dose dependently decreased the immobility period in mice. ED(50) values of imipramine, fluoxetine, and venlafaxine in FST and TST were found to be 9.2 and 10 mg/kg i.p, 18 and 20 mg/kg, i.p., and 8.5 and 12 mg/kg, i.p respectively. The relative potency of standard drugs in both FST and TST is imipramine=venlafaxine>fluoxetine. Mianserin (16 and 32 mg/kg., i.p.) or trazodone (1 and 2 mg/kg., i.p.) were ineffective to reduce the immobility period in both the tests showing the atypical nature of these antidepressants. Chlorpromazine or pentobarbitone was ineffective in reversing the immobility period thus validating the models for testing antidepressants. The present study further validated that both the test procedures are equi-sensitive to antidepressant drugs of different class in the strain of animals used.
强迫游泳试验（FST）和悬尾试验（TST）被广泛用作筛选潜在抗抑郁药的动物模型。FST和TST中产生的不动或绝望行为被视为抑郁的范例，抗抑郁药可减少不动时间。最近的研究表明这两种模型在血流动力学、行为、生理和药理学方面存在不同的变化。此外，研究还提出了品系在这些绝望模型中的重要性，试图在不同实验室之间重复实验结果。本研究旨在使用雄性Laca小鼠比较四类主要抗抑郁药即三环类药物（丙咪嗪）、选择性5-羟色胺再摄取抑制剂（氟西汀）、5-羟色胺和去甲肾上腺素双重再摄取抑制剂（文拉法辛）以及非典型抗抑郁药（米安色林和曲唑酮）的抗抑郁作用，以验证这两种测试方法。在两个试验的6分钟期间记录总不动时间，结果以相对于赋形剂对照的不动时间减少百分比表示。氯丙嗪（4mg/kg，腹腔注射）或戊巴比妥（20mg/kg，腹腔注射）用作阴性对照。丙咪嗪（2、5、10和20mg/kg）、氟西汀（5、10、20和40mg/kg）或文拉法辛（2、4、8和16mg/kg）剂量依赖性地减少小鼠的不动时间。在FST和TST中，丙咪嗪（imipramine）、氟西汀（fluoxetine）和文拉法辛（venlafaxine）的半数有效量（ED50）分别为腹腔注射9.2和10mg/kg、18和20mg/kg以及8.5和12mg/kg。标准药物在FST和TST中的相对效价为丙咪嗪=文拉法辛>氟西汀。米安色林（16和32mg/kg，腹腔注射）或曲唑酮（1和2mg/kg，腹腔注射）在两个试验中均不能有效减少不动时间，显示出这些抗抑郁药的非典型性质。氯丙嗪或戊巴比妥不能有效逆转不动时间，从而验证了用于测试抗抑郁药的模型。本研究进一步验证了在所用动物品系中，这两种测试方法对不同类别的抗抑郁药具有同等敏感性。
