title: Extracellular signal-regulated kinase 5 in the cerebrospinal fluid-contacting nucleus contributes to morphine physical dependence in rats.
abstract: The cerebrospinal fluid-contacting nucleus (CSF-CN) may influence actual composition of the CSF for non-synaptic signal transmission via releasing or absorbing bioactive substances, which distributes and localizes in the ventral periaqueductal central gray of the brainstem. Previous studies demonstrated that CSF-CN was involved in neuropathic pain and morphine dependence. Thus, to identify whether extracellular signal-regulated kinase 5 (ERK5) distributed in the CSF-CN and its function on the formation and development of morphine physical dependence, morphine withdrawal-like behavioral test and immunofluorescent technique were used in this research. Morphine was subcutaneously injected by an intermittent and escalating procedure to induce physical dependence, which was measured by withdrawal symptoms. In this study, we found that horseradish peroxidase-conjugated toxin subunit B/p-ERK5 double-labeled neurons expressed in the CSF-CN of normal rats. ERK5 signaling pathway was remarkably activated by naloxone-precipitated withdrawal in the CSF-CN. Moreover, selective attenuation of p-ERK5 expression in the CSF-CN by lateral ventricle injection of BIX02188 could significantly relieve morphine withdrawal symptom. These findings confirmed that the activation of p-ERK5 in the CSF-CN might contribute to morphine physical dependence.
authors.affiliation: Department of Anesthesiology, The First Center Hospital of Bao Ding, Baoding 071000, Hebei, China.
authors.forename: Chun-Guang
authors.initials: CG
authors.lastname: Wang
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Ding
authors.forename: Tian-Fang
authors.initials: TF
authors.lastname: Zheng
authors.forename: Jing-Qiu
authors.initials: JQ
authors.lastname: Wei
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Chen
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Wang
authors.forename: Li-Cai
authors.initials: LC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002555:Cerebrospinal Fluid / Q000166:cytology; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D009020:Morphine / Q000633:toxicity*; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000633:toxicity*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism*
chemical_list: D009294:Narcotics; D009270:Naloxone; D009020:Morphine; D048054:Mitogen-Activated Protein Kinase 7