CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy
CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy
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DOI：
10.1007/s00213-011-2169-8
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发表时间：
2011-06-01
影响因子：
3.4
通讯作者：
Oenguer, Dost
中科院分区：
文献类型：
--
作者：
Bechtholt-Gompf, Anita J.;Smith, Karen L.;Oenguer, Dost
在患者中，氯胺酮是一种快速有效的抗抑郁剂，可以诱导持久的症状缓解。在啮齿动物中也有类似的快速效应报告，但关于持续影响的报告有限。我们试图通过检查与先前报告的在啮齿动物中引起持久影响的个体剂量重叠的剂量-反应曲线来扩展过去的发现，并确定影响是否推广到尾部悬吊试验(TST)和Balb/CJ小鼠。使用抗抑郁药效的常见测试，我们首先证实了我们检测地昔帕明的效果的能力，地昔帕明是一种特征良好的抗抑郁药物。接下来，我们试图确定两种非竞争性NMDA拮抗剂氯胺酮和MK-801在CD-1小鼠身上是否具有长期的抗抑郁药样作用，这种菌株经常被用来证明氯胺酮的短期抗抑郁药样作用。最后，我们研究了氯胺酮在对抗抑郁药样作用更敏感的小鼠品系Balb/CJ小鼠身上的短期和长期效应。在CD-1小鼠中，地昔帕明治疗在TST和强迫游泳试验(FST)中产生了显著的短期抗抑郁药样作用。然而，1周后，氯胺酮或MK-801没有明显的持久效应。在Balb/CJ小鼠中观察到氯胺酮在TST中的短期效应，但1周后没有持久效应。尽管TST和FST已被广泛用于检测小鼠的抗抑郁药样效应，但它们似乎对小鼠的长期抗抑郁药样效应不敏感，因此不能模拟氯胺酮在患有严重抑郁症的人类中的治疗效果。
In patients, ketamine is a fast-acting antidepressant that can induce long-lasting symptom relief. Similar rapid effects have been reported in rodents, but reports of lasting effects are limited.We sought to extend past findings by examining dose-response curves that overlap with the individual doses previously reported to induce lasting effects in rodents and determining whether effects generalize to the tail suspension test (TST) and Balb/cJ mice.Using common tests of antidepressant efficacy we first confirmed our ability to detect the effects of desipramine, a well-characterized antidepressant drug. Next, we sought to determine whether two non-competitive NMDA antagonists, ketamine and MK-801, had long-lasting antidepressant-like effects in CD-1 mice, a strain that has often been used to demonstrate the short-term antidepressant-like effects of ketamine. Finally, we examined the short- and long-term effects of ketamine in a mouse strain that is more sensitive to antidepressant-like effects, Balb/cJ mice.In CD-1 mice, desipramine treatment yielded significant short-term antidepressant-like effects in the TST and the forced swimming test (FST). However, no significant enduring effects of ketamine or MK-801 were observed 1 week later. Short-term effects of ketamine in the TST were observed in Balb/cJ mice, but lasting effects were absent 1 week later.Although the TST and FST have been widely used to detect antidepressant-like effects in mice, they do not appear to be sensitive to long-lasting antidepressant-like effects of ketamine in mice and, therefore, do not model the therapeutic effects of ketamine that have been reported in humans with major depression.