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

Han Zhang; Jieting Yin; Lei Jia; Xinlei Qin; Tongyu Du; Ketao Ma; Jiangwen Yin; Yan Li

doi:10.1016/j.sleep.2022.08.020

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

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

Authors

Han Zhang¹, Jieting Yin¹, Lei Jia¹, Xinlei Qin¹, Tongyu Du¹, Ketao Ma², Jiangwen Yin³, Yan Li⁴

Affiliations

¹ 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.
² Department of Physiology, School of Medicine, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University, Shihezi, China.
³ 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. Electronic address: yjw6654328@163.com.
⁴ 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. Electronic address: 1249623003@qq.com.

PMID: 36148759
DOI: 10.1016/j.sleep.2022.08.020

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: 1. 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.

Keywords: Anxiety; Dopamine transporter; Electroencephalogram; Propofol; Sleep deprivation; VTA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anesthesia*
Animals
Dopamine Plasma Membrane Transport Proteins / pharmacology
Male
Propofol* / pharmacology
Rats
Rats, Sprague-Dawley
Sleep
Sleep Deprivation
Ventral Tegmental Area

Substances

Propofol
Dopamine Plasma Membrane Transport Proteins