title: Hydrogen-rich saline attenuates anxiety-like behaviors in morphine-withdrawn mice.
abstract: Hydrogen therapy is a new medical approach for a wide range of diseases. The effects of hydrogen on central nervous system-related diseases have recently become increasingly appreciated, but little is known about whether hydrogen affects the morphine withdrawal process. This study aims to investigate the potential effects of hydrogen-rich saline (HRS) administration on naloxone-precipitated withdrawal symptoms and morphine withdrawal-induced anxiety-like behaviors. Mice received gradually increasing doses (25-100 mg/kg, i.p.) of morphine over 3 days. In the naloxone-precipitated withdrawal procedure, the mice were treated with three HRS (20 μg/kg, i.p.) injections, and naloxone (1 mg/kg, i.p.) was given 30 min after HRS administration. Body weight, jumping behavior and wet-dog shakes were immediately assessed. In the spontaneous withdrawal procedure, the mice were treated with HRS (20 μg/kg, i.p.) every 8-h. Mice underwent naloxone-precipitated or spontaneous withdrawal were tested for anxiety-like behaviors in the elevated plus-maze (EPM) and light/dark box (L/D box) paradigm, respectively. In addition, the levels of plasma corticosterone were measured. We found that HRS administration significantly reduced body weight loss, jumping behavior and wet-dog shakes in mice underwent naloxone-precipitated withdrawal, and attenuated anxiety-like behaviors in the EPM and L/D box tests after naloxone-precipitated withdrawal or a 2-day spontaneous withdrawal period. Hypo-activity or motor impairment after HRS administration was not observed in the locomotion tests. Furthermore, HRS administration significantly decreased the levels of corticosterone in morphine-withdrawn mice. These are the first findings to indicate that hydrogen might ameliorate withdrawal symptoms and exert an anxiolytic-like effect in morphine-withdrawal mice.
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Wen
authors.affiliation: College of Basic Medicine, Hebei Medical University, Hebei Province, Shijiazhuang 050017, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: College of Basic Medicine, Hebei Medical University, Hebei Province, Shijiazhuang 050017, PR China.
authors.forename: Rongji
authors.initials: R
authors.lastname: Hui
authors.affiliation: College of Basic Medicine, Hebei Medical University, Hebei Province, Shijiazhuang 050017, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China.
authors.forename: Qianchao
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Histoembryology, Hebei Medical University, Hebei Province, Shijiazhuang 050017, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Gong
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China. Electronic address: hbydbincong@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Cong
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China. Electronic address: chunlingma@126.com.
authors.forename: Chunling
authors.initials: C
authors.lastname: Ma
mesh_terms: D000221:Adaptation, Ocular / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019416:Head Movements / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood; D006859:Hydrogen / Q000627:therapeutic use*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000627:therapeutic use; D012965:Sodium Chloride / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D013375:Substance Withdrawal Syndrome / Q000150:complications* / Q000188:drug therapy
chemical_list: D014151:Anti-Anxiety Agents; D009270:Naloxone; D012965:Sodium Chloride; D009020:Morphine; D006859:Hydrogen; D003345:Corticosterone; D006854:Hydrocortisone
keywords: Anxiety-like behavior; Hydrogen-rich saline; Hypothalamic-pituitary-adrenal axis; Molecular hydrogen; Morphine withdrawal