Koek Wouter, Sandoval Thomas L, Daws Lynette C
Departments of Psychiatry.
Pharmacology.
Behav Pharmacol. 2018 Aug;29(5):453-456. doi: 10.1097/FBP.0000000000000371.
The forced swim test in rodents allows rapid detection of substances with antidepressant-like activity, evidenced as a decreased duration of immobility that is produced by the majority of clinically used antidepressants. Antidepressants also increase the latency to immobility, and this additional measure reportedly can increase the sensitivity of the forced swim test in mice. Extending these findings, the present study examined the effects of desipramine and fluvoxamine in a forced swim test in C57BL/6J mice, a strain commonly used as background for genetic modifications, analyzing results with a method (i.e. survival analysis) that can model the skewed distribution of latencies and that can deal with censored data (i.e. when immobility does not occur during the test), in comparison with the more traditional Student's t-test. Desipramine increased the latency to immobility at 32 mg/kg, but not at lower doses. Fluvoxamine also did not affect latency at lower doses, but in contrast to desipramine, fluvoxamine decreased the latency to immobility at the highest dose (i.e. 32 mg/kg). At doses affecting latency to immobility, neither desipramine nor fluvoxamine significantly affected duration of immobility. Together, these results are generally consistent with the suggestion that inclusion of the latency measure can increase the sensitivity of the forced swim test to detect antidepressant-like effects in mice.
啮齿动物的强迫游泳试验能够快速检测出具有抗抑郁样活性的物质,大多数临床使用的抗抑郁药可使不动时间缩短,这证明了该试验的有效性。抗抑郁药还会增加不动潜伏期,据报道,这一额外指标可提高小鼠强迫游泳试验的敏感性。基于这些研究结果,本研究检测了地昔帕明和氟伏沙明在C57BL/6J小鼠强迫游泳试验中的作用,C57BL/6J小鼠是常用于基因改造背景的品系,本研究采用一种方法(即生存分析)分析结果,该方法可以对潜伏期的偏态分布进行建模,并且可以处理删失数据(即在试验期间未出现不动情况),并与更传统的学生t检验进行比较。地昔帕明在32mg/kg时增加了不动潜伏期,但在较低剂量时没有。氟伏沙明在较低剂量时也不影响潜伏期,但与地昔帕明不同的是,氟伏沙明在最高剂量(即32mg/kg)时缩短了不动潜伏期。在影响不动潜伏期的剂量下,地昔帕明和氟伏沙明均未显著影响不动时间。总之,这些结果总体上与以下观点一致,即纳入潜伏期指标可以提高强迫游泳试验检测小鼠抗抑郁样效应的敏感性。