Persistent stress increases the probability for developing depression significantly thereafter. Repeated social defeat stress is a widely used model to investigate depressive-like behavior in preclinical models. Hence, the repeated social defeat stress model provided an ideal animal model, through which the hypotheses of prevention and treatment can be investigated. We have successfully induced depressive-like behavior for male C57BL/6J mice with this model. Here, we reported that certain level of during-stress social interactions with single female or multiple male peer(s) exerted a positive role in preventing the development of depressive-like behavior induced by repeated social defeat stress. Our data suggested that the stress-susceptible mice may benefit from positive social interaction, which reduces the chance for depressive-like behavior development. Since numerous studies indicate that the metabotropic glutamate receptor 5 (mGluR5) plays an important role in various cognitive functions, we further investigate the treatment effect of 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) on the depressive-like behavior induced by repeated social defeat stress. Most importantly, robust anti-depressant effects have been achieved through modulating the mGluR5 function. We found that single oral dose administration of CDPPB (20 mg/kg), to some extent, alleviated the social avoidance behaviors for the stress-susceptible mice. Our data implies that the CDPPB, a positive allosteric modulator of mGluR5, is a promising anti-depressant candidate with limited side effect.

持续的压力会显着增加此后患抑郁症的可能性。重复的社交失败压力是一种广泛使用的模型，用于研究临床前模型中的抑郁样行为。因此，重复的社会失败应激模型提供了一个理想的动物模型，通过它可以研究预防和治疗的假设。我们已经用该模型成功诱导了雄性 C57BL/6J 小鼠的抑郁样行为。在这里，我们报告说，在压力期间与单个女性或多个男性同伴进行一定程度的社交互动，对于防止反复的社交失败压力引起的抑郁样行为的发展发挥了积极作用。我们的数据表明，对压力敏感的小鼠可能会​​受益于积极的社交互动，从而减少出现抑郁样行为的机会。由于大量研究表明代谢型谷氨酸受体 5 (mGluR5) 在各种认知功能中发挥重要作用，因此我们进一步研究 3-cyano-N-(1,3-二苯基-1H-pyrazol-5-yl) 的治疗效果苯甲酰胺（CDPPB）对反复社交失败压力引起的抑郁样行为的影响。最重要的是，通过调节 mGluR5 功能实现了强大的抗抑郁作用。我们发现单剂量口服CDPPB（20 mg/kg）在一定程度上减轻了应激易感小鼠的社交回避行为。我们的数据表明 CDPPB（mGluR5 的正变构调节剂）是一种有前途的抗抑郁候选药物，副作用有限。