Gabapentinoids, which are the common analgesics, are also thought to be an effective treatment for anxiety disorder, which is one of several psychiatric disorders triggered and exacerbated by stress. The aim of the present study was to investigate whether mirogabalin, a recently launched gabapentinoid, protects multiple brain functions against repeated restraint stress. Adult male ddY mice were restrained for 7 days (repeated restraint stress: 2 h/day) or for 30 min (single restraint stress). Mirogabalin (intraperitoneal, intracerebroventricular or intrahippocampal injection) was administered prior to the restraint stress. Y-maze, elevated-plus maze and c-Fos immunohistochemistry were performed to evaluate learning function, anxiety levels and hippocampal neuronal activities, respectively, after the 7th day of the repeated restraint stress. Intestinal function was evaluated in terms of defecation, which was scored after the 5th day of repeated restraint stress and by the number of fecal pellets excreted after a single session of restraint stress. Repeated restraint stress induced memory dysfunction, anxiety-like behavior, an abnormal defecation score and increased hippocampal c-Fos expression. These changes were prevented by systemic administration of mirogabalin. Abnormal defecation was also induced by single restraint stress, and was inhibited by both systemic and central administration of mirogabalin, suggesting that the effect on the intestinal function was also mediated via the central nervous system. Enhancement of c-Fos expression by repeated stress was decreased by intrahippocampal injection of mirogabalin. Together, these observations suggest that mirogabalin protects multiple brain functions from repeated stress, which may be mediated by inhibition of hippocampal neuron hyperactivation.

中文翻译：

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米罗巴林可防止小鼠反复束缚应激引起的功能障碍。

加巴喷丁是常见的镇痛药，也被认为是治疗焦虑症的有效方法，焦虑症是由压力引起并加重的几种精神疾病之一。本研究的目的是研究米洛巴林（一种最近启动的加巴喷丁胺）是否能保护多种脑功能免受反复的约束压力。成年雄性ddY小鼠被限制7天（重复约束压力：2小时/天）或30分钟（单个约束压力）。束缚应激前先给予米格巴林（腹膜内，脑室内或海马注射）。重复约束应激的第7天后，分别进行Y迷宫，升高迷宫和c-Fos免疫组化评估学习功能，焦虑水平和海马神经元活动。根据排便评估肠道功能，排便是在反复施加约束力的第5天后进行排便，并通过在单个约束应力后排泄的粪便颗粒的数量进行评分。反复施加约束压力会导致记忆功能障碍，焦虑样行为，排便评分异常和海马c-Fos表达增加。通过米罗巴林的全身性给药可以防止这些改变。单一约束压力也可引起排便异常，米罗巴林的全身和中央给药均可抑制排便异常，这表明对肠道功能的影响也通过中枢神经系统介导。海马内注射米罗巴林可降低反复应激引起的c-Fos表达增强。一起，