title: Gentiopicroside attenuates morphine rewarding effect through downregulation of GluN2B receptors in nucleus accumbens.
abstract: OBJECTIVE
  Gentiopicroside (Gent) is one of the secoiridoid compound isolated from Gentiana lutea. This compound exhibits analgesic activities and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cortex in mice. Nucleus accumbens (NAc) is a forebrain structure known for its role in drug addiction. However, little is known about the role of Gent on morphine dependence and synaptic transmission changes in the NAc.
  
  
  METHODS
  Conditioned place preference (CPP) test and behavioral sensitization of locomotor activity were used to investigate drug-seeking related behaviors. Brain slices containing NAc were prepared, and whole-cell patch-clamp recordings were performed to record the excitatory postsynaptic currents (EPSCs). Expression of proteins was detected by Western blot analysis.
  
  
  RESULTS
  Systemic administration of Gent attenuated the CPP effect induced by morphine, but had no effect on morphine-induced behavioral sensitization. Gent significantly reversed overexpression of GluN2B-containing NMDA receptors and dopamine D2 receptors in NAc during the first week of morphine withdrawal. However, the compound did not affect the overexpression of GluN2A-containing NMDA receptors, GluA1, and dopamine D1 receptors. Lastly, Gent significantly reduced NMDA receptors-mediated EPSCs in the NAc.
  
  
  CONCLUSIONS
  Our study provides strong evidence that Gent inhibits morphine dependence through downregulation of GluN2B-containing NMDA receptors in the NAc.
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, China.
authors.forename: Shui-Bing
authors.initials: SB
authors.lastname: Liu
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Guo
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Guo
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Li
authors.forename: Wen-Ji
authors.initials: WJ
authors.lastname: Sun
authors.forename: Lian-He
authors.initials: LH
authors.lastname: Zheng
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Zhao
mesh_terms: D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy / Q000523:psychology; D015153:Blotting, Western; D003216:Conditioning, Operant / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D057888:Iridoid Glucosides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000187:drug effects; D012201:Reward
chemical_list: D000701:Analgesics, Opioid; D057888:Iridoid Glucosides; C121001:NR2B NMDA receptor; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; C012997:gentiopicroside; D009020:Morphine