Department of Psychiatry, Harvard Medical School-McLean Hospital, 115 Mill Street, MRC 215, Belmont, MA 02478, USA.
Psychopharmacology (Berl). 2011 Jun;215(4):689-95. doi: 10.1007/s00213-011-2169-8. Epub 2011 Jan 28.
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.
在患者中，氯胺酮是一种快速起效的抗抑郁药，可诱导持久的症状缓解。在啮齿动物中也有类似的快速作用的报道，但持续作用的报道有限。
我们试图通过检查与先前报道的在啮齿动物中诱导持久作用的个体剂量重叠的剂量-反应曲线，来扩展过去的发现，并确定这些作用是否推广到悬尾试验（TST）和 Balb/cJ 小鼠。
使用常见的抗抑郁疗效测试，我们首先确认了我们检测去甲丙咪嗪作用的能力，去甲丙咪嗪是一种经过充分研究的抗抑郁药物。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，是否对 CD-1 小鼠具有持久的抗抑郁样作用，CD-1 小鼠是一种常用于显示氯胺酮短期抗抑郁样作用的品系。最后，我们研究了氯胺酮在更敏感的抗抑郁样作用的 Balb/cJ 小鼠中的短期和长期作用。
在 CD-1 小鼠中，去甲丙咪嗪治疗在 TST 和强迫游泳试验（FST）中产生了显著的短期抗抑郁样作用。然而，1 周后没有观察到氯胺酮或 MK-801 的持久作用。在 Balb/cJ 小鼠中观察到氯胺酮在 TST 中的短期作用，但 1 周后没有持久作用。
尽管 TST 和 FST 已广泛用于检测小鼠中的抗抑郁样作用，但它们似乎对氯胺酮在小鼠中的持久抗抑郁样作用不敏感，因此不能模拟在患有重度抑郁症的人类中报告的氯胺酮的治疗效果。
