BDNF is a negative modulator of morphine action.
BDNF is a negative modulator of morphine action.
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DOI：
10.1126/science.1222265
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发表时间：
2012-10-05
期刊：
影响因子：
--
通讯作者：
Nestler EJ
中科院分区：
文献类型：
--
作者：
Koo JW;Mazei-Robison MS;Chaudhury D;Juarez B;LaPlant Q;Ferguson D;Feng J;Sun H;Scobie KN;Damez-Werno D;Crumiller M;Ohnishi YN;Ohnishi YH;Mouzon E;Dietz DM;Lobo MK;Neve RL;Russo SJ;Han MH;Nestler EJ
脑源性神经营养因子（BDNF）是神经可塑性的关键正调节因子，促进例如滥用的兴奋剂药物（如可卡因）的作用。我们发现了BDNF在对抗慢性吗啡反应方面的惊人相反作用。抑制腹侧被盖区（VTA）的BDNF可增强吗啡增加多巴胺（DA）神经元兴奋性和促进奖赏的能力。相反，光刺激腹侧被盖区中脑腹外侧核（NAc）的DA能末梢可完全逆转BDNF对吗啡奖赏的抑制作用。此外，我们确定了NAc中的许多基因，NAc是腹侧被盖区DA神经元的主要靶区域，其在慢性吗啡暴露的背景下由BDNF调节介导了这种反作用功能。这些发现提供了深入了解吗啡诱导的大脑奖励回路神经适应的分子基础。
Brain-derived neurotrophic factor (BDNF) is a key positive regulator of neural plasticity, promoting for example, the actions of stimulant drugs of abuse such as cocaine. We discovered a surprising opposite role for BDNF in countering responses to chronic morphine. The suppression of BDNF in the ventral tegmental area (VTA) enhanced the ability of morphine to increase dopamine (DA) neuron excitability and promote reward. In contrast, optical stimulation of VTA DA terminals in nucleus accumbens (NAc) completely reversed the suppressive effect of BDNF on morphine reward. Furthermore, we identified numerous genes in NAc, a major target region of VTA DA neurons, whose regulation by BDNF in the context of chronic morphine exposure mediated this counteractive function. These findings provide insight into the molecular basis of morphine-induced neuroadaptations in the brain’s reward circuitry.
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