Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse
Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse
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DOI：
10.1038/nn1929
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发表时间：
2007-08-01
影响因子：
25
通讯作者：
Self, David W.
中科院分区：
文献类型：
--
作者：
Graham, Danielle L.;Edwards, Scott;Self, David W.
单次接触可卡因会迅速诱导几个即刻早期基因的短暂激活，但对这种短期调节在可卡因使用的持久后果中的作用知之甚少。我们发现，4小时的静脉内可卡因自我管理在大鼠中诱导脑源性神经营养因子（BDNF）和激活TrkB介导的信号转导在延髓核（NAc）的短暂增加。每天输注五次NAc脑源性神经营养因子来增强这种动态调节，会导致可卡因自我给药的持续增加，并促进戒断时可卡因寻求的复发。与此相反，中和内源性BDNF调节与内NAc输注抗体BDNF随后减少可卡因自我管理和衰减复发。利用小鼠中的局部诱导型BDNF敲除，我们发现源自NAc神经元的BDNF对于维持增加的可卡因自我给药是必要的。这些发现表明，在可卡因使用过程中，NAc神经元动态诱导和释放BDNF促进成瘾行为的发展和持续。
A single exposure to cocaine rapidly induces the brief activation of several immediate early genes, but the role of such short-term regulation in the enduring consequences of cocaine use is poorly understood. We found that 4 h of intravenous cocaine self-administration in rats induced a transient increase in brain-derived neurotrophic factor (BDNF) and activation of TrkB-mediated signaling in the nucleus accumbens (NAc). Augmenting this dynamic regulation with five daily NAc BDNF infusions caused enduring increases in cocaine self-administration, and facilitated relapse to cocaine seeking in withdrawal. In contrast, neutralizing endogenous BDNF regulation with intra-NAc infusions of antibody to BDNF subsequently reduced cocaine self-administration and attenuated relapse. Using localized inducible BDNF knockout in mice, we found that BDNF originating from NAc neurons was necessary for maintaining increased cocaine self-administration. These findings suggest that dynamic induction and release of BDNF from NAc neurons during cocaine use promotes the development and persistence of addictive behavior.