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多巴胺能中脑边缘系统活动与抑郁行为的解码

Decoding of dopaminergic mesolimbic activity and depressive behavior.

作者信息

Friedman Alexander, Deri Ilana, Friedman Yaakov, Dremencov Eliyahu, Goutkin Sophia, Kravchinsky Elizabeth, Mintz Matti, Levi Dino, Overstreet David H, Yadid Gal

机构信息

Leslie Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel.

出版信息

J Mol Neurosci. 2007;32(1):72-9. doi: 10.1007/s12031-007-0016-5.

Abstract

Dopaminergic mesolimbic and mesocortical systems are involved in hedonia and motivation, two core symptoms of depression. However, their role in the pathophysiology of depression and their manipulation to treat depression has received little attention. Previously, we showed decreased limbic dopamine (DA) neurotransmission in an animal model of depression, Flinder sensitive line (FSL) rats. Here we describe a high correlation between phase-space algorithm of bursting-like activity of DA cells in the ventral tegmental area (VTA) and efficiency of DA release in the accumbens. This bursting-like activity of VTA DA cells of FSL rats is characterized by a low dimension complexity. Treatment with the antidepressant desipramine affected both the dimension complexity of cell firing in the VTA and rate of DA release in the accumbens, as well as alleviating depressive-like behavior. Our findings indicate the potential usefulness of monitoring limbic dopaminergic dynamics in combination with non-linear analysis. Decoding the functionality of the dopaminergic system may help in development of future antidepressant drugs.

摘要

多巴胺能中脑边缘系统和中脑皮质系统参与享乐和动机,这是抑郁症的两个核心症状。然而,它们在抑郁症病理生理学中的作用以及通过调控它们来治疗抑郁症的研究却很少受到关注。此前,我们在抑郁症动物模型弗林德敏感系(FSL)大鼠中发现边缘多巴胺(DA)神经传递减少。在此,我们描述了腹侧被盖区(VTA)中DA细胞爆发样活动的相空间算法与伏隔核中DA释放效率之间的高度相关性。FSL大鼠VTA DA细胞的这种爆发样活动具有低维度复杂性的特征。用抗抑郁药地昔帕明治疗既影响VTA中细胞放电的维度复杂性和伏隔核中DA释放速率,又能减轻抑郁样行为。我们的研究结果表明结合非线性分析监测边缘多巴胺能动力学具有潜在的实用性。解码多巴胺能系统的功能可能有助于未来抗抑郁药物的研发。

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