title: Orexin-A facilitates emergence of the rat from isoflurane anesthesia via mediation of the basal forebrain.
abstract: Previous studies have demonstrated that orexinergic neurons involve in promoting emergence from anesthesia of propofol, an intravenous anesthetics, while whether both of orexin-A and orexin-B have promotive action on emergence via mediation of basal forebrain (BF) in isoflurane anesthesia has not been elucidated. In this study, we observed c-Fos expressions in orexinergic neurons following isoflurane inhalation (for 0, 30, 60, and 120min) and at the time when the righting reflex returned after the cessation of anesthesia. The plasma concentrations of orexin-A and -B in anesthesia-arousal process were measured by radioimmunoassay. Orexin-A and -B (30 or 100pmol) or the orexin receptor-1 and -2 antagonist SB-334867A and TCS-OX2-29 (5 or 20μg) were microinjected into the basal forebrain respectively. The effects of them on the induction (loss of the righting reflex) and the emergence time (return of the righting reflex) under isoflurane anesthesia were observed. The results showed that the numbers of c-Fos-immunoreactive orexinergic neurons in the hypothalamus decreased over time with continued isoflurane inhalation, but restored at emergence. Similar alterations were observed in changes of plasma orexin-A concentrations but not in orexin-B during emergence. Administration of orexins had no effect on the induction time, but orexin-A facilitated the emergence of rats from isoflurane anesthesia while orexin-B didn't. Conversely, microinjection of the orexin receptor-1 antagonist SB-334867A delayed emergence from isoflurane anesthesia. The results indicate that orexin-A plays a promotive role in the emergence of isoflurane anesthesia and this effect is mediated by the basal forebrain.
authors.affiliation: Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases, Education Ministry, Xian Jiaotong University School of Medicine, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: Cen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: Peng-Rong
authors.initials: PR
authors.lastname: Ouyang
authors.affiliation: Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases, Education Ministry, Xian Jiaotong University School of Medicine, China.
authors.forename: Zhi-Chao
authors.initials: ZC
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: Ming-Zi
authors.initials: MZ
authors.lastname: Ran
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, China. Electronic address: hldong6@hotmail.com.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Dong
authors.affiliation: Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases, Education Ministry, Xian Jiaotong University School of Medicine, China. Electronic address: liuy5599@mail.xjtu.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D000818:Animals; D066187:Basal Forebrain / Q000187:drug effects* / Q000378:metabolism*; D001583:Benzoxazoles / Q000008:administration & dosage; D007530:Isoflurane / Q000008:administration & dosage*; D008297:Male; D009287:Naphthyridines; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D000068796:Orexin Receptor Antagonists / Q000008:administration & dosage; D000068797:Orexins / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D018685:Anesthetics, Inhalation; D001583:Benzoxazoles; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D014508:Urea; D007530:Isoflurane
keywords: Basal forebrain; Emergence time; Isoflurane anesthesia; Orexins