Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China.
Department of Anesthesiology, Affiliated Hospital of Nanjing, University of Traditional Chinese Medicine, Nanjing, China.
Eur Psychiatry. 2015 Jun;30(4):504-10. doi: 10.1016/j.eurpsy.2014.11.007. Epub 2015 Mar 18.
Current available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.
目前可用的抗抑郁药显示出低缓解率和长反应滞后时间。越来越多的证据表明，急性亚麻醉剂量的氯胺酮具有快速、强大和持久的抗抑郁作用。然而，长期使用氯胺酮往往会引起不良反应。本研究旨在探讨间歇性和连续给予氯胺酮对慢性不可预测轻度应激（CUMS）大鼠的抗抑郁样作用，并确定氯胺酮是否可以弥补经典抗抑郁药治疗反应的时间滞后。通过蔗糖偏好测试、强迫游泳测试和旷场测试评估行为反应。在实验的第一阶段，氯胺酮的所有四种治疗方案（10mg/kg ip，连续 3 或 7 天每天一次，或每 7 或 3 天一次，共 21 天）均表现出强大的抗抑郁样作用，对 CUMS 大鼠的运动活性和刻板行为无明显影响。间歇性给药方案产生的抗抑郁样作用比连续给药方案长，且每 7 天给药一次与每 3 天给药一次相比，具有相似的抗抑郁样作用且给药次数更少。在实验的第二阶段，氯胺酮（10mg/kg ip，每 7 天一次）与西酞普兰（20mg/kg po，每天一次）联合应用 21 天，引起的抗抑郁样作用比单独使用西酞普兰更快、更持久。总之，重复给予亚麻醉剂量的氯胺酮可以弥补西酞普兰抗抑郁样作用的时间滞后，这表明氯胺酮与经典抗抑郁药的联合应用是一种有前途的治疗方案，可以快速起效，效果稳定持久。
