腹侧被盖区多巴胺转运体对睡眠剥夺大鼠异丙酚麻醉后睡眠恢复的影响。

Effects of dopamine transporter in the ventral tegmental area on sleep recovery after propofol anesthesia in sleep-deprived rats.

机构信息

Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832000, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, School of Medicine, Shihezi University, China.

Department of Physiology, School of Medicine, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University, Shihezi, China.

出版信息

Sleep Med. 2022 Dec;100:269-279. doi: 10.1016/j.sleep.2022.08.020. Epub 2022 Sep 8.

DOI:10.1016/j.sleep.2022.08.020

PMID:36148759

Abstract

OBJECTIVE

Previous studies indicate that propofol can help with recovery from sleep deprivation and has anti-anxiety effects. However, the underlying neurochemical mechanism remains unclear. This study aimed to investigate the effects of dopamine transporter (DAT) in the ventral tegmental area (VTA) on sleep and anxiety recovery after propofol anesthesia in rats with 24 h total sleep deprivation (TSD).

METHODS

Adult male Sprague-Dawley rats were in natural sleep or sleep deprived for 24 h in a sleep deprivation rat system. The rats received propofol anesthesia (75 mg/kg, i.p.) or natural sleep. Dopamine transporter knockdown was performed by microinjection of AAV-DAT-RNAi vector. EEG was measured in each group to evaluate the subsequent sleep. The elevated plus maze test (EPMT) and open field test (OFT) were used to evaluate locomotion and anxiety level in rats. Immunofluorescence was used to verify virus location and transfection efficiency.

RESULTS

Compared with NC group, the anxiety level of Propofol group showed no significant difference, but REM sleep decreased. Compared with the TSD group, the anxiety level of the TSD + Propofol group was reduced and the sleep recovery was closer to baseline. Compared with TSD + AAV-NC group, anxiety level and sleep time increased in TSD + AAVi group, REM increased within 24 h after sleep deprivation. The sleep time of TSD + AAVi + Propofol group was between those of TSD + AAV-NC group and TSD + AAVi group. TSD + AAV-NC + Propofol group had the least sleep time and the lowest anxiety level.

CONCLUSION

Propofol did not change anxiety level in normal rats, but reduced REM sleep, while it could accelerate sleep recovery and reduce anxiety level in sleep-deprived rats. 2. In sleep deprived rats with DAT knockdown, propofol improved sleep and anxiety levels more slowly, especially producing more REM rebound, suggesting that the improvement of sleep and anxiety levels in sleep-deprived rats with propofol may be related to DAT in VTA region.

摘要

目的

先前的研究表明，异丙酚有助于从睡眠剥夺中恢复，并且具有抗焦虑作用。然而，其潜在的神经化学机制尚不清楚。本研究旨在探讨腹侧被盖区（VTA）多巴胺转运体（DAT）对 24 小时总睡眠剥夺（TSD）大鼠异丙酚麻醉后睡眠和焦虑恢复的影响。

方法

成年雄性 Sprague-Dawley 大鼠在睡眠剥夺大鼠系统中自然睡眠或睡眠剥夺 24 小时。大鼠接受异丙酚麻醉（75mg/kg，ip）或自然睡眠。通过注射 AAV-DAT-RNAi 载体进行多巴胺转运体敲低。在各组中测量脑电图以评估随后的睡眠。高架十字迷宫试验（EPMT）和旷场试验（OFT）用于评估大鼠的运动和焦虑水平。免疫荧光用于验证病毒位置和转染效率。

结果

与 NC 组相比，Propofol 组的焦虑水平无显著差异，但 REM 睡眠减少。与 TSD 组相比，TSD+Propofol 组的焦虑水平降低，睡眠恢复更接近基线。与 TSD+AAV-NC 组相比，TSD+AAVi 组的焦虑水平和睡眠时间增加，REM 在睡眠剥夺后 24 小时内增加。TSD+AAVi+Propofol 组的睡眠时间介于 TSD+AAV-NC 组和 TSD+AAVi 组之间。TSD+AAV-NC+Propofol 组睡眠时间最短，焦虑水平最低。