title: The ventrolateral preoptic nucleus is required for propofol-induced inhibition of locus coeruleus neuronal activity.
abstract: The mechanisms underlying the unconsciousness of general anesthesia are not completely understood. Accumulating evidence indicates the ventrolateral preoptic nucleus (VLPO) in the endogenous sleep circuits may contribute to loss of consciousness (LOC) induced by GABA-enhancing anesthetics. However, there are few studies that look into distinct sleep pathway in the sleep-wake system. In the neural pathway from VLPO to the locus coeruleus (LC), we compared the inhibition effect of propofol on the LC activity before and after VLPO lesion in vivo rats. Systemic administration of propofol (20 mg/kg, i.p.) in normal rats caused a fast and obvious inhibition of LC neurons spontaneous firing (from 0.24 ± 0.06 to 0.12 ± 0.03 Hz). The LC neuronal firing rate of VLPO lesion rats only decreased to 0.18 ± 0.05 Hz (P = 0.021 vs. non-VLPO rats) after the propofol injection, and the time to reach the maximal inhibition level was also prolonged in VLPO lesion rats (2.3 ± 0.7 vs. 5.8 ± 1.2 min, P = 0.037). Microinjections of a selective GABAA receptor antagonist (SR95531) into the LC fully reversed the inhibitory effect of propofol on the LC neuronal activity, but did not significantly affect the latency to loss of righting reflex of rats after propofol administration (3.4 ± 0.9 vs. 3.7 ± 1.2 min, P = 0.639). Our results indicated that VLPO is necessary for the propofol-induced inhibition of LC activity, but the LC may not play an important role in the propofol-induced LOC.
authors: Guizhou Key Laboratory of Anesthesia and Organ Protection, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, People's Republic of China. gytzhangyu@163.com.|Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Ruijin Er Road 197, Shanghai, 200025, People's Republic of China. gytzhangyu@163.com.
authors: Yu
authors: Y
authors: Zhang
authors: Guizhou Key Laboratory of Anesthesia and Organ Protection, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, People's Republic of China.
authors: Tian
authors: T
authors: Yu
authors: Guizhou Key Laboratory of Anesthesia and Organ Protection, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, People's Republic of China.
authors: Jie
authors: J
authors: Yuan
authors: Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Ruijin Er Road 197, Shanghai, 200025, People's Republic of China. ruijinyubuwei@163.com.
authors: Bu-Wei
authors: BW
authors: Yu
mesh_terms: D000818:Animals; D004569:Electroencephalography / Q000379:methods; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D011301:Preoptic Area / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects / Q000502:physiology
chemical_list: D009294:Narcotics; D015742:Propofol
keywords: Consciousness; General anesthesia; Locus coeruleus; Propofol; Ventrolateral preoptic