title: D-Serine in the nucleus accumbens region modulates behavioral sensitization and extinction of conditioned place preference.
abstract: BACKGROUND
  D-serine, the endogenous co-agonist of N-methyl-D-aspartate receptors (NMDARs), is considered to be essential for learning and memory. The aim of the current investigation was to systematically evaluate the role of D-serine on addiction behaviors considered to be mediated by the nucleus accumbens (NAc).
  
  
  METHODS
  D-Serine concentration in the NAc was measured by high-performance liquid chromatography (HPLC). Cocaine-induced behavioral sensitization and conditioned place preference (CPP) models were used to evaluate the relation between changes in serine in the nucleus accumbens and cocaine-induced behavioral effects. The expression of serine racemase (SR), D-amino acid oxidase (DAAO), the cAMP response element-binding protein (CREB) and upstream kinases, and N-methyl-D-aspartate (NMDA) receptors subunits were analyzed by western blot. Long-term depression (LTD) in the NAc was investigated by electrophysiological methods.
  
  
  RESULTS
  The NAc slices obtained from the behavioral sensitization rats presented significantly reduced D-serine concentrations, increased expression of DAAO, and down-regulated expression of SR in a dose-dependent manner. Furthermore, D-serine injections into the nucleus accumbens blocked the development of behavioral sensitization and caused extinction of CPP. The ERK-CREB-Fos pathway and the NMDA receptor NR2B subunits in the NAc were involved in the cocaine-induced behavioral sensitization. We also found that D-serine was essential for NMDAR-dependent LTD and D-serine-regulated LTD in a bell-shaped concentration-dependent manner. The disrupted NMDAR-dependent LTD in the NAc of cocaine-treated rats was reversed by D-serine.
  
  
  CONCLUSIONS
  Our results provide evidence for a critical role of D-serine in synaptic plasticity relevant to cocaine addiction and indicate that D-serine may be an effective therapeutic agent for cocaine addiction.
authors: Department of Neurology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China; Cadre of Neurology, Jiangxi People's Hospital, Nanchang, Jiangxi, China; Department of Medical Experimental Center, Jiangxi Mental Hospital, Nanchang, Jiangxi, China.
authors: Zhi-Qiang
authors: ZQ
authors: Liu
authors: Department of Neurology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China; Department of Medical Experimental Center, Jiangxi Mental Hospital, Nanchang, Jiangxi, China.
authors: Xun-Hu
authors: XH
authors: Gu
authors: Department of Medical Experimental Center, Jiangxi Mental Hospital, Nanchang, Jiangxi, China.
authors: Yuan-Jian
authors: YJ
authors: Yang
authors: Department of Neurology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.
authors: Xiao-ping
authors: XP
authors: Yin
authors: Department of Neurology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. Electronic address: xulijun20050901@sina.com.
authors: Li-Jun
authors: LJ
authors: Xu
authors: Department of Neurology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. Electronic address: wuhansy@126.com.
authors: Wei
authors: W
authors: Wang
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D003214:Conditioning, Classical; D004305:Dose-Response Relationship, Drug; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism*
chemical_list: D012694:Serine; D003042:Cocaine
keywords: Behavioral sensitization; Cocaine; Conditioned place preference; Nucleus accumbens; d-Serine