Rationale

Major depressive disorder (MDD) is a debilitating disorder with adverse effects on mood, memory, and quality of life.

Objectives

In this study, the antidepressant potential of glatiramer acetate (GA), a drug used in the management of multiple sclerosis, was investigated in acute and chronic models of depression in male mice. The acute antidepressant screening was performed with the forced swim (FST) and tail suspension (TST) tests. In the chronic phase, post-weaning social isolation (SI) was used to induce depressive-/anxiety-like behaviors.

Methods

Mice were reared in two different groups of social (SG) and isolated (IG) for 4 weeks. IG mice were treated with 0.5, 1.0, and 2.0 mg/kg of GA for the last 2 weeks of the SI period. Animals were assessed by the behavioral tests of depression, anxiety, learning, and memory, and hippocampal brain-derived neurotrophic factor (BDNF) level was measured.

Results

The acute tests confirmed the antidepressant potential of GA. In the chronic phase, GA could reduce immobility time in FST (P < 0.05), increase exploration activity in open field test (P < 0.05), increase open arms duration (P < 0.05) and entries in elevated plus maze (P<0.001), and improve memory and learning in passive avoidance test (P < 0.05). The BDNF level was increased in IG mice and decreased in IG mice treated with GA.

Conclusions

Our results showed that GA improved depressive-/anxiety-like behaviors and cognitive dysfunction of SI reared mice without increasing the BDNF level which may be associated with other mechanisms of actions of GA.

中文翻译：

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醋酸格拉默可减轻雄性小鼠断奶后社会隔离引起的抑郁/焦虑样行为和认知缺陷

 基本原理

重度抑郁症 (MDD) 是一种使人衰弱的疾病，会对情绪、记忆力和生活质量产生不利影响。

 目标

在这项研究中，在雄性小鼠的急性和慢性抑郁模型中研究了醋酸格拉替雷 (GA) 的抗抑郁潜力，这种药物用于治疗多发性硬化症。通过强迫游泳（FST）和悬尾（TST）测试进行急性抗抑郁药筛查。在慢性阶段，断奶后社会隔离（SI）被用来诱发抑郁/焦虑样行为。

 方法

小鼠在社会组 (SG) 和隔离组 (IG) 两个不同组中饲养 4 周。在 SI 期的最后 2 周，用 0.5、1.0 和 2.0 mg/kg 的 GA 治疗 IG 小鼠。通过抑郁、焦虑、学习记忆等行为测试来评估动物，并测量海马脑源性神经营养因子（BDNF）水平。

 结果

急性试验证实了 GA 的抗抑郁潜力。在慢性期，GA可以减少FST中的不动时间（ P < 0.05），增加旷场测试中的探索活动（ P < 0.05），增加张开手臂的持续时间（ P < 0.05）和高架十字迷宫的进入时间（P< 0.05）。 P <0.001），并提高被动回避测试中的记忆和学习能力（ P < 0.05）。 IG 小鼠的 BDNF 水平升高，而 GA 治疗的 IG 小鼠的 BDNF 水平降低。

 结论

我们的结果表明，GA 改善了 SI 饲养的小鼠的抑郁/焦虑样行为和认知功能障碍，而没有增加 BDNF 水平，这可能与 GA 的其他作用机制有关。