In this study, we investigated the ability of a single coadministration of subeffective doses of ascorbic acid and ketamine to reverse the depressive-like behavior induced by chronic unpredictable stress (CUS) in mice. Moreover, we examined the effect of combined administration of ascorbic acid and ketamine on hippocampal phosphorylation of p70S6K and immunocontents of GLUA1 and PSD-95 in mice submitted to the CUS procedure. CUS procedure was applied for 21 days. Animals received a single coadministration of subeffective doses of ascorbic acid (0.1 mg/kg) and ketamine (0.1 mg/kg) and were subjected to behavioral evaluation 24 h after the treatments. Immediately after the behavioral observations the hippocampi were dissected for Western blotting analyses. Our results revealed that a single administration of subeffective doses of ascorbic acid and ketamine completely reversed the depressive-like behavior induced by CUS, however, this effect was not accompanied by changes in the phosphorylation of p70S6K and immunocontent of GLUA1 or PSD95 in the hippocampus. These findings point to a synergistic antidepressant-like effect of ascorbic acid and ketamine, paving the way for additional studies on the combined use of these compounds for the management of major depressive disorder (MDD).

在这项研究中，我们调查了亚有效剂量的抗坏血酸和氯胺酮的单次联合给药逆转小鼠慢性不可预测压力（CUS）引起的抑郁样行为的能力。此外，我们检查了抗坏血酸和氯胺酮联合给药对提交CUS程序的小鼠海马p70S6K磷酸化以及GLUA1和PSD-95免疫含量的影响。进行CUS程序21天。动物接受亚有效剂量的抗坏血酸（0.1 mg / kg）和氯胺酮（0.1 mg / kg）的单次共同给药，并在治疗后24小时进行行为评估。观察到行为后，立即解剖海马以进行蛋白质印迹分析。我们的研究结果表明，单次使用亚有效剂量的抗坏血酸和氯胺酮完全可以逆转CUS诱导的抑郁样行为，但是，这种作用并未伴随p70S6K磷酸化以及海马GLUA1或PSD95免疫含量的变化。这些发现表明抗坏血酸和氯胺酮具有类似抗抑郁药的协同作用，为进一步研究这些化合物联合用于治疗重性抑郁症（MDD）铺平了道路。