Life and Health Science Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
Transl Psychiatry. 2013 Jun 4;3(6):e266. doi: 10.1038/tp.2013.39.
There is accumulating evidence that the nucleus accumbens (NAc) has an important role in the pathophysiology of depression. As the NAc is a key component in the neural circuitry of reward, it has been hypothesized that anhedonia, a core symptom of depression, might be related to dysfunction of this brain region. Neuronal morphology and expression of plasticity-related molecules were examined in the NAc of rats displaying anhedonic behavior (measured in the sucrose-consumption test) in response to chronic mild stress. To demonstrate the relevance of our measurements to depression, we tested whether the observed changes were sensitive to reversal with antidepressants (imipramine and fluoxetine). Data show that animals displaying anhedonic behavior display an hypertrophy of medium spiny neurons in the NAc and, in parallel, have increased expression of the genes encoding for brain-derived neurotrophic factor, neural cell adhesion molecule and synaptic protein synapsin 1. Importantly, the reversal of stress-induced anhedonia by antidepressants is linked to a restoration of gene-expression patterns and dendritic morphology in the NAc. Using an animal model of depression, we show that stress induces anhedonic behavior that is associated with specific changes in the neuronal morphology and in the gene-expression profile of the NAc that are effectively reversed after treatment with antidepressants.
越来越多的证据表明，伏隔核（NAc）在抑郁症的病理生理学中起着重要作用。由于 NAc 是奖励神经回路的关键组成部分，因此有人假设，快感缺失，即抑郁症的核心症状，可能与该大脑区域的功能障碍有关。为了证明我们的测量与抑郁症有关，我们测试了观察到的变化是否对抗抑郁药（丙咪嗪和氟西汀）的逆转敏感。数据表明，表现出快感缺失行为的动物在 NAc 中显示出中等棘突神经元的肥大，并且，平行地，编码脑源性神经营养因子，神经细胞粘附分子和突触蛋白突触素 1 的基因的表达增加。重要的是，抗抑郁药对应激引起的快感缺失的逆转与 NAc 中基因表达模式和树突形态的恢复有关。使用抑郁症动物模型，我们表明应激会引起快感缺失行为，这与 NAc 中的神经元形态和基因表达谱的特定变化有关，这些变化在用抗抑郁药治疗后得到有效逆转。
