Department of Psychology Weifang Medical University Shandong China.
School of Bioscience and Technology Weifang Medical University Shandong China.
Brain Behav. 2017 Jun 23;7(8):e00749. doi: 10.1002/brb3.749. eCollection 2017 Aug.
This research was aimed to evaluate the behaviors of short- or long-term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS).
Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory.
After 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43-75). The influence of ketamine on behavioral reactivity was assessed 24 hr (short-term) or 7 weeks after ketamine treatment (long-term). Behavioral tests used to assess the effects of these treatments included the sucrose preference (SP), open field (OF), elevated plus maze (EPM), forced swimming (FS), and water maze (WM) to detect anxiety-like behavior (OF and EPM), forced swimming (FS), and water maze (WM). Results: Short-term ketamine administration resulted in increases of body weight gain, higher sensitivity to sucrose, augmented locomotor activity in the OF, more entries into the open arms of the EPM, along increased activity in the FS test; all responses indicative of reductions in depression/despair in anxiety-eliciting situations. No significant differences in these behaviors were obtained under conditions of long-term ketamine administration ( > .05). The CUS + Ketamine group showed significantly increased activity as compared with the CUS + Vehicle group for analysis of the long-term effects of ketamine (* < .05). Nor were significant differences obtained in learning and memory performance in rats receiving ketamine ( > .05).
Taken together these findings demonstrate that a short-term administration of ketamine induced rapid antidepressant-like effects in adult male rats exposed to CUS conditions, effects that were not observed in response to the long-term treatment regime.
本研究旨在评估氯胺酮对慢性不可预测应激（CUS）大鼠的短期或长期抗抑郁作用行为。
氯胺酮是一种谷氨酸非竞争性 NMDA 受体拮抗剂，调节兴奋性氨基酸功能，如焦虑障碍和重性抑郁症，在突触可塑性和学习记忆中发挥重要作用。
在 CUS 模型 42 天后，雄性大鼠接受单次氯胺酮注射（10mg/kg；第 43 天）或 15 次每日注射（第 43-75 天）。氯胺酮对行为反应的影响在氯胺酮治疗后 24 小时（短期）或 7 周（长期）进行评估。用于评估这些治疗效果的行为测试包括蔗糖偏好（SP）、旷场（OF）、高架十字迷宫（EPM）、强迫游泳（FS）和水迷宫（WM），以检测焦虑样行为（OF 和 EPM）、强迫游泳（FS）和水迷宫（WM）。结果：短期氯胺酮给药导致体重增加、对蔗糖的敏感性增加、OF 中的运动活动增加、EPM 的开放臂进入次数增加、FS 测试中的活动增加；所有这些反应都表明在焦虑诱发的情况下减少了抑郁/绝望。在长期氯胺酮给药（>0.05）条件下，这些行为没有显著差异。与 CUS+Vehicle 组相比，CUS+Ketamine 组在分析氯胺酮的长期作用时表现出明显增加的活动（*<0.05）。接受氯胺酮的大鼠在学习和记忆表现方面也没有显著差异（>0.05）。
综上所述，这些发现表明，短期给予氯胺酮可诱导暴露于 CUS 条件的成年雄性大鼠快速抗抑郁样作用，而长期治疗方案则没有观察到这种作用。
