Differential roles of hippocampal glutamatergic receptors in neuropathic anxiety-like behavior after partial sciatic nerve ligation in rats

BMC Neuroscience

Fang-Fang Bi¹  Zhi-Yuan Li³  Chang-Qi Li³  Zhou Xin-Fu⁴  Ru-Ping Dai²  Jian-Yi Zhang³  Fang Li³  Juan Zhang³  Hong-Tao Wang³  Zhi-Bin Li¹  Xiao-Lin Zhong³  Xue-Qin Wang³ 

[1] Department of Neurology, XiangYa Hospital, Central South University, XiangYa Road 88, Changsha, Hunan, China;Department of Anesthesia, the Second XiangYa Hospital of Central South University, Ren-Min Road 86, Changsha, Hunan, China;Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Tongzipo Road 172, Changsha, Hunan, China;School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide 5000, SA, Australia

关键词: Rats;    Anxiety;    Glutamatergic receptor;    Hippocampus;    Neuropathic pain;   

Others  :  1170557
DOI  :  10.1186/s12868-015-0150-x

 received in 2014-10-16, accepted in 2015-02-25,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Wang et al.; licensee BioMed Central.

【 图 表 】

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