Open AccessGentiopicroside Attenuates Morphine Rewarding Effect through Downregulation of GluN2B Receptors in Nucleus Accumbens
Author(s) -
Liu ShuiBing,
Ma Lan,
Guo HongJu,
Feng Bin,
Guo YanYan,
Li XiaoQiang,
Sun WenJi,
Zheng LianHe,
Zhao MingGao
Publication year - 2012
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/j.1755-5949.2012.00338.x
Subject(s) - nucleus accumbens , nmda receptor , conditioned place preference , pharmacology , chemistry , morphine , excitatory postsynaptic potential , receptor , sensitization , dopamine , downregulation and upregulation , glutamate receptor , forebrain , neuroscience , psychology , biology , biochemistry , central nervous system , gene
SUMMARY Aims: 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. Conclusion: Our study provides strong evidence that Gent inhibits morphine dependence through downregulation of GluN2B‐containing NMDA receptors in the NAc.