Infection and Immunology Research Laboratory, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, China, 646000.
Psychiatry Res. 2011 Jan 30;185(1-2):248-53. doi: 10.1016/j.psychres.2010.04.046. Epub 2010 May 23.
Animal and clinical studies have demonstrated that ketamine has quick, obvious and persistent antidepressant-like effect, but such side effects as cardiovascular system excitement and hallucinogenic activity have limited its clinical application. Intravenous anesthetic propofol can remarkably inhibit or eliminate ketamine's side effects including cardiovascular system excitement and hallucinogenic activity even in a sub-anesthesia dose. However, effect of propofol on rapid antidepressant-like action induced by ketamine still remains unclear. The present study aimed to investigate effect of pretreatment with propofol on the ketamine-induced rapid antidepressant-like action in rats receiving forced swimming test. Open field test and forced swimming test were used to investigate behavior changes of rats receiving different medication. Expression of brain derived neurotrophic factors (BDNF) and a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) pGluR1-Ser845 in hippocampus was measured with sandwich-ELISA and Western Blot, respectively. Results demonstrated that rats receiving propofol alone showed neither antidepressant-like effects nor increased BDNF content; pretreatment with propofol could increase the ketamine-induced antidepressant-like effects and the expression of AMPA pGluR1-Ser845 in hippocampus, but could not further reinforce the increased BDNF content induced by ketamine in hippocampus; after AMPA receptor was antagonized, the strengthening effect of propofol on ketamine-induced antidepressant-like action significantly decreased. The results indicated that propofol in a sub-anesthetic dose could increase the ketamine-induced antidepressant-like effect.
动物和临床研究表明，氯胺酮具有快速、明显和持久的抗抑郁样作用，但心血管兴奋和致幻活性等副作用限制了其临床应用。静脉麻醉药异丙酚可以显著抑制或消除氯胺酮的副作用，包括心血管兴奋和致幻活性，即使在亚麻醉剂量下也是如此。然而，异丙酚对氯胺酮引起的快速抗抑郁样作用的影响仍不清楚。本研究旨在探讨异丙酚预处理对接受强迫游泳试验的大鼠氯胺酮诱导的快速抗抑郁样作用的影响。旷场试验和强迫游泳试验用于研究接受不同药物的大鼠的行为变化。采用夹心酶联免疫吸附试验和 Western blot 分别测量海马脑源性神经营养因子（BDNF）和 a-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）pGluR1-Ser845 的表达。结果表明，单独给予异丙酚的大鼠既没有抗抑郁样作用，也没有增加 BDNF 含量；异丙酚预处理可以增加氯胺酮诱导的抗抑郁样作用和海马 AMPA pGluR1-Ser845 的表达，但不能进一步增强氯胺酮诱导的海马 BDNF 含量的增加；在 AMPA 受体被拮抗后，异丙酚对氯胺酮诱导的抗抑郁样作用的增强作用明显降低。结果表明，亚麻醉剂量的异丙酚可以增加氯胺酮诱导的抗抑郁样作用。
