- 作者：Bo Jiang ; Wei Wang ; Fang Wang ; Zhuang-Li Hu ; Jun-Li Xiao ; Si Yang ; Jing Zhang ; Xiao-Zhong Peng ; Jin-Hui Wang ; Jian-Guo Chen
- 关键词：Chronic social defeat stress ; depression ; hippocampal neurogenesis ; long-term depression ; NMDA ; NR2B ; nucleus accumbens
- 刊名：Biological Psychiatry
- 出版年：2013
- 出版时间：15 July, 2013
- 年：2013
- 卷：74
- 期：2
- 页码：145-155
- 全文大小：2209 K
Background
The nucleus accumbens (NAc) is closely correlated with depression. It has been demonstrated that the glutamatergic system in NAc plays an important role in the reward pathway, dysfunction of which would cause anhedonia, a core symptom of depression. We therefore tested whether N-methyl-D-aspartate receptors and the synaptic plasticity in the NAc are regulated by chronic stress and the relevance to depression.Methods
We applied behavioral tests (n = 12, each group) of social interaction and sucrose preference tests to identify the susceptibility of mice to chronic social defeat stress. We then tested N-methyl-D-aspartate receptor-long-term depression at cortico-accumbal synapse to determine the relationship between the susceptibility and changes in synaptic plasticity (n = 8, each group). We further investigated whether restoration of these changes could produce antidepressant effects (n = 10).
Results
We found that chronic stress induced selective downregulation of N-methyl-D-aspartate receptor NR2B subunits in the confined surface membrane pool of NAc neurons. Remarkably, the loss of synaptic NR2B was a long-lived event and further translated to the significant modulation of synaptic plasticity in the form of long-term depression. We further observed that the stress-induced changes were restored by fluoxetine and that resilient mice¡ªthose resistant to chronic stress¡ªshowed patterns of molecular regulation in the NAc that overlapped dramatically with those seen with fluoxetine treatment. Behaviorally, restoration of NR2B loss prevented the behavioral sensitization of mice to chronic stress.
Conclusions
Our results identify NR2B in the NAc as a key regulator in the modulation of persistent psychomotor plasticity in response to chronic stress.