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右美托咪定改善睡眠剥夺诱导的小鼠抑郁行为。

Dexmedetomidine Ameliorates Sleep Deprivation-Induced Depressive Behaviors in Mice.

作者信息

Moon Eun-Jin, Ko Il-Gyu, Kim Sung-Eun, Jin Jun-Jang, Hwang Lakkyong, Kim Chang-Ju, An Hyeonjun, Lee Bong-Jae, Yi Jae-Woo

机构信息

Department of Anesthesiology and Pain Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea.

Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.

出版信息

Int Neurourol J. 2018 Oct;22(Suppl 3):S139-146. doi: 10.5213/inj.1836228.114. Epub 2018 Oct 31.

Abstract

PURPOSE

Sleep deprivation induces depressive symptoms. Dexmedetomidine is a α2-adrenoreceptor agonist and this drug possesses sedative, anxiolytic, analgesic, and anesthetic-sparing effect. In this study, the action of dexmedetomidine on sleep deprivation-induced depressive behaviors was investigated using mice.

METHODS

For the inducing of sleep deprivation, the mice were placed inside a water cage containing 15 platforms and filled with water up to 1 cm below the platform surface for 7 days. One day after sleep deprivation, dexmedetomidine at the respective dosage (0.5, 1, and 2 μg/kg) was intraperitoneally treated into the mice, one time per a day during 6 days. Then, forced swimming test and tail suspension test were conducted. Immunohistochemistry for tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT; serotonin), tryptophan hydroxylase (TPH) and western blot for D1 dopamine receptor were also performed.

RESULTS

Sleep deprivation increased the immobility latency in the forced swimming test and tail suspension test. The expressions of TPH, 5-HT, and D1 dopamine receptor were decreased, whereas, TH expression was increased by sleep deprivation. Dexmedetomidine decreased the immobility latency and increased the expressions of TPH, 5-HT, and D1 dopamine receptor, whereas, HT expression was decreased by dexmedetomidine treatment.

CONCLUSION

In our results, dexmedetomidine alleviated sleep deprivation-induced depressive behaviors by increasing 5-HT synthesis and by decreasing dopamine production with up-regulation of D1 dopamine receptor.

摘要

目的

睡眠剥夺可诱发抑郁症状。右美托咪定是一种α2肾上腺素能受体激动剂,该药物具有镇静、抗焦虑、镇痛和节省麻醉的作用。在本研究中,使用小鼠研究了右美托咪定对睡眠剥夺诱导的抑郁行为的作用。

方法

为诱导睡眠剥夺,将小鼠置于装有15个平台的水笼中,水充满至平台表面以下1厘米,持续7天。睡眠剥夺一天后,将相应剂量(0.5、1和2μg/kg)的右美托咪定腹腔注射给小鼠,在6天内每天一次。然后,进行强迫游泳试验和悬尾试验。还进行了酪氨酸羟化酶(TH)、5-羟色胺(5-HT;血清素)、色氨酸羟化酶(TPH)的免疫组织化学和D1多巴胺受体的蛋白质免疫印迹分析。

结果

睡眠剥夺增加了强迫游泳试验和悬尾试验中的不动时间。睡眠剥夺使TPH、5-HT和D1多巴胺受体的表达降低,而TH表达增加。右美托咪定缩短了不动时间,增加了TPH、5-HT和D1多巴胺受体的表达,而右美托咪定处理使HT表达降低。

结论

在我们的研究结果中,右美托咪定通过增加5-HT合成和减少多巴胺生成以及上调D1多巴胺受体来减轻睡眠剥夺诱导的抑郁行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7727/6234724/07edebc8c7a7/inj-1836228-114f1.jpg

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