Purpose

Histamine H₃ receptor ligands may have antidepressant and anxiolytic effects. They can also compensate for metabolic disorders, which affect glucose or triglyceride levels. In previous studies, we have shown that pitolisant, a histamine H₃ receptor antagonist/inverse agonist and σ1 receptor agonist, prevented the development of certain metabolic and depressive-like disorders in mice that have been treated chronically with olanzapine.

Methods

As a continuation of our previous experiments, this study aimed to investigate the antidepressant- and anxiolytic-like activity of pitolisant in mice using the corticosterone-induced depression model. The forced swim and the elevated plus maze tests were used as behavioral endpoints. We also studied the effect pitolisant had on the level of acetoacetic acid in the urine as well as the glucose tolerance and body weight of the mice that had been administered corticosterone.

Results

Pitolisant (10 mg/kg b.w.) did not prevent depressive-like behavior in mice during the chronic corticosterone administration but did counteract anxiety-like behavior, whilst fluoxetine (10 mg/kg) was shown to protect the mice from both of these behaviors. None of the treatments that were used in the study showed an effect on the locomotor activity of the mice. Pitolisant did not prevent an increase in acetoacetic acid levels in the urine, nor did it improve glucose tolerance in the tested mice.

Conclusion

Although literature data indicates that there is significant potential for finding an antidepressant and anti-diabetic drug among the histamine H₃ and σ1 receptor ligands, in our study, pitolisant was shown to only slightly compensate for corticosterone-induced abnormalities. However, further research will be required to study pitolisant's anxiolytic-like activity.

中文翻译：

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Pitolisant保护长期接受皮质酮治疗的小鼠免受皮质酮诱导的抑郁模型的某些行为改变，但不能代谢。

目的

组胺H ₃受体配体可能具有抗抑郁和抗焦虑作用。它们还可以补偿影响葡萄糖或甘油三酸酯水平的代谢异常。在以前的研究中，我们已经证明，匹兹列斯坦（组胺H ₃受体拮抗剂/反向激动剂和σ1受体激动剂）可以预防已用奥氮平进行长期治疗的小鼠某些新陈代谢和抑郁样疾病的发展。

方法

作为我们先前实验的延续，本研究旨在研究使用皮质酮诱发的抑郁症模型中pitolisant在小鼠中的抗抑郁和抗焦虑样活性。强迫游泳和高架迷宫测试被用作行为终点。我们还研究了pitolisant对尿液中乙酰乙酸水平以及已给予皮质酮的小鼠的葡萄糖耐量和体重的影响。

结果

Pitolisant（10 mg / kg bw）不能在长期服用皮质酮期间预防小鼠的抑郁样行为，但可以抵消焦虑样行为，而氟西汀（10 mg / kg）被证明可以保护小鼠免受这两种行为的影响。该研究中使用的任何一种治疗方法均未显示对小鼠运动能力的影响。Pitolisant不能阻止尿液中乙酰乙酸水平的增加，也不能改善测试小鼠的葡萄糖耐量。

结论

尽管文献数据表明，在组胺H ₃和σ1受体配体中发现抗抑郁药和抗糖尿病药的潜力很大，但在我们的研究中，皮果酸药仅能轻微补偿皮质酮引起的异常。然而，将需要进一步的研究来研究匹罗替尼的抗焦虑样活性。