title: Differential roles of hippocampal glutamatergic receptors in neuropathic anxiety-like behavior after partial sciatic nerve ligation in rats.
abstract: BACKGROUND
  Neuropathic pain evoked by nerve injury is frequently accompanied by deterioration of emotional behaviors, but the underlying signaling mechanisms remain elusive. Glutamate (Glu) is the major mediator of excitatory synaptic transmission throughout the brain, and abnormal activity of the glutamatergic system has been implicated in the pathophysiology of pain and associated emotional comorbidities. In this study we used the partial sciatic nerve ligation (PSNL) model of neuropathic pain in rats to characterize the development of anxiety-like behavior, the expression of glutamatergic receptors, and the phosphorylation of extracellular signal-regulated kinase (ERK) in the hippocampus, the region that encodes memories related to emotions.
  
  
  RESULTS
  We found that the mechanical withdrawal threshold was significantly reduced and an anxiety-like behavior was increased as determined via open field tests and elevated plus-maze tests at 28 days after injury. No significant differences were found in the ratio of sucrose preference and immobility time detected by sucrose preference tests and forced swimming tests respectively, possibly due to the timing factor. The expression of N-methyl-D-aspartate (NMDA) receptor subtypes NR1 and NR2B, but not NR2A, GluR1, or GluR2 (the main subtype of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] receptor) in the hippocampus of injured rats was significantly reduced. Moreover, PSNL resulted in decreased phosphorylation of ERK1/2 in the hippocampus. Intriguingly, treatment with D-serine (a co-agonist of NMDA receptor, 1 g/kg intraperitoneally) reduced the anxiety-like behavior but not the mechanical hypersensitivity induced by PSNL.
  
  
  CONCLUSIONS
  PSNL can induce significant anxiety-like but not depression-like behavior, and trigger down-regulation of NMDA but not AMPA receptors in the hippocampus at 28 days after injury.
authors.affiliation: Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha, Hunan, China. 524483503@qq.com.|Department of Anesthesiology, the Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha, Hunan, China. 524483503@qq.com.|Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Tongzipo Road 172, Changsha, Hunan, China. 524483503@qq.com.
authors.forename: Xue-Qin
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Tongzipo Road 172, Changsha, Hunan, China. 709829504@qq.com.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Zhong
authors.affiliation: Department of Neurology, XiangYa Hospital, Central South University, XiangYa Road 88, Changsha, Hunan, China. 610751680@qq.com.
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Li
authors.affiliation: Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Tongzipo Road 172, Changsha, Hunan, China. 1571801193@qq.com.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Tongzipo Road 172, Changsha, Hunan, China. 863303394@qq.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Tongzipo Road 172, Changsha, Hunan, China. fangli@csu.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Tongzipo Road 172, Changsha, Hunan, China. zhangjy@csu.edu.cn.
authors.forename: Jian-Yi
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, the Second XiangYa Hospital of Central South University, Ren-Min Road 86, Changsha, Hunan, China. 909025585@qq.com.
authors.forename: Ru-Ping
authors.initials: RP
authors.lastname: Dai
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA, 5000, Australia. zhou0010@gmail.com.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xin-Fu
authors.affiliation: Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Tongzipo Road 172, Changsha, Hunan, China. changqili@csu.edu.cn.
authors.forename: Chang-Qi
authors.initials: CQ
authors.lastname: Li
authors.affiliation: Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Tongzipo Road 172, Changsha, Hunan, China. lizhiyuan@csu.edu.cn.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Neurology, XiangYa Hospital, Central South University, XiangYa Road 88, Changsha, Hunan, China. bffxyneurology@163.com.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Bi
mesh_terms: D059445:Anhedonia / Q000187:drug effects / Q000502:physiology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*; D012584:Sciatic Nerve / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D012694:Serine / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D019422:Dietary Sucrose; D017470:Receptors, Glutamate; D012694:Serine