title: Dexmedetomidine Dose-Dependently Attenuates Ropivacaine-Induced Seizures and Negative Emotions Via Inhibiting Phosphorylation of Amygdala Extracellular Signal-Regulated Kinase in Mice.
abstract: Ropivacaine (Ropi), one of the newest and safest amino amide local anesthetics, is linked to toxicity, including the potential for seizures, changes in behavior, and even cardiovascular collapse. Dexmedetomidine (Dex), an α2-adrenergic receptor agonist, has been widely used in anesthesia and critical care practice. To date, the underlying mechanisms of the effects of Dex premedication on Ropi-induced toxicity have not been clearly identified. In the current study, we investigated the effects of increasing doses of Dex premedication on 50% convulsive dose (CD50) of Ropi. With increasing doses of intraperitoneal (i.p.) Dex 10 min prior to each i.p. RopiCD50, the latency and duration of seizure activity were recorded. Open-field (OF) and elevated plus maze (EPM) test were used to measure negative behavioral emotions such as depression and anxiety. Immunohistochemistry and Western blot were utilized to investigate phosphorylation-extracellular regulated protein kinases (p-ERK) expression in the basolateral amygdala (BLA) on 2 h and in the central amygdala (CeA) on 24 h after convulsion in mice. The results of our investigation demonstrated that Dex dose-dependently increased RopiCD50, prolonged the latency and shortened the duration of each RopiCD50-induced seizure, improved the negative emotions revealed by both OF and EPM test, and inhibited p-ERK expression in the BLA and the CeA.
authors.affiliation: Department of Medical Psychology, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Ming-Zhu
authors.initials: MZ
authors.lastname: Zhai
authors.affiliation: Department of Anesthesiology, Fuzhou General Hospital of Nanjing Military Region, No.156, North of West Second Ring Rd, Gulou District, Fuzhou, 350025, China.
authors.forename: Huang-Hui
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Department of Anatomy & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jun-Bin
authors.initials: JB
authors.lastname: Yin
authors.affiliation: Institution of Basic Medical Science and Lab of Cell Biology & Translational Medicine, Xi'an Medical University, Xi'an, 710032, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Cui
authors.affiliation: Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Mei
authors.affiliation: Department of Anatomy & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medical Psychology, Fourth Military Medical University, Xi'an, 710032, China. zhuxia@fmmu.edu.cn.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Occupational and Environmental Health and the Ministry of Education's Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, 710032, China. xfshen@fmmu.edu.cn.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Shen
authors.affiliation: Departments of Anesthesiology and Pharmacology, Louisiana State University School of Medicine, Room 656, 1542 Tulane Ave., New Orleans, LA, 70112, USA. alankaye44@hotmail.com.
authors.forename: Alan David
authors.initials: AD
authors.lastname: Kaye
authors.affiliation: Department of Anesthesiology, Fuzhou General Hospital of Nanjing Military Region, No.156, North of West Second Ring Rd, Gulou District, Fuzhou, 350025, China. cgzssq2000@sina.com.
authors.forename: Guo-Zhong
authors.initials: GZ
authors.lastname: Chen
mesh_terms: D000577:Amides; D000679:Amygdala / Q000201:enzymology* / Q000473:pathology*; D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D000077212:Ropivacaine; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D000577:Amides; D020927:Dexmedetomidine; D000077212:Ropivacaine; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Basolateral amygdala; Central amygdala; Convulsion; Dexmedetomidine; Negative emotion; Ropivacaine; p-ERK