Endogenous BDNF in the dorsolateral striatum gates alcohol drinking.
Endogenous BDNF in the dorsolateral striatum gates alcohol drinking.
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DOI：
10.1523/jneurosci.2243-09.2009
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发表时间：
2009-10-28
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影响因子：
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通讯作者：
Ron D
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文献类型：
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作者：
Jeanblanc J;He DY;Carnicella S;Kharazia V;Janak PH;Ron D
我们以前发现，脑源性神经营养因子（BDNF）单倍缺陷小鼠表现出更大的乙醇诱导的位置偏好和精神敏感，以及剥夺后更大的乙醇消耗。我们进一步观察到，在小鼠中，自愿摄入乙醇增加背侧纹状体（DS）中BDNF的表达。在这里，我们确定是否BDNF的DS调节乙醇自我管理在长埃文斯大鼠训练自我管理的10%乙醇溶液。我们观察到一个更大的增加后，乙醇自我管理的背外侧纹状体（DLS）比背内侧纹状体（DMS）的BDNF表达。我们进一步发现，在DLS中使用病毒介导的siRNA下调内源性BDNF，而不是在DMS中，显著增加乙醇自我给药。当在自我给药阶段开始前3小时输注外源性BDNF（DMS中0.25 μg/μl/侧; DLS中0.25和0.75 μg/μl/侧）时，可减弱对乙醇的反应。虽然在DLS和DMS中乙醇摄入量的减少是相似的，但在DLS中而不是在DMS中注入BDNF诱导了饮酒事件的提前终止。此外，BDNF在DLS中的作用对乙醇是特异性的，因为在DMS中而不是DLS中输注神经营养因子导致蔗糖摄入量减少。总之，这些发现表明，在DLS内的BDNF途径控制乙醇自我管理的水平。重要的是，我们的研究结果表明，在同一个大脑区域内，介导吸毒行为的内源性信号通路在控制乙醇摄入水平方面也起着关键作用。
We previously found that brain-derived neurotrophic factor (BDNF) haplodeficient mice exhibit greater ethanol-induced place preference and psychomotor sensitization, and greater ethanol consumption after deprivation. We further observed that, in mice, voluntary ethanol intake increases BDNF expression in the dorsal striatum (DS). Here, we determined whether BDNF within the DS regulates ethanol self-administration in Long Evans rats trained to self-administer a 10% ethanol solution. We observed a greater increase in BDNF expression after ethanol self-administration in the dorsolateral striatum (DLS) than in the dorsomedial striatum (DMS). We further found that downregulation of endogenous BDNF using viral-mediated siRNA in the DLS, but not in the DMS, significantly increased ethanol self-administration. Infusion of exogenous BDNF (0.25 μg/μl/side into the DMS; 0.25 and 0.75 μg/μl/side into the DLS) attenuated responding for ethanol when infused 3 hrs prior to the beginning of the self-administration session. Although the decrease in ethanol intake was similar in the DLS and DMS, BDNF infused in the DLS but not in the DMS induced an early termination of the drinking episode. Furthermore, the action of BDNF in the DLS was specific for ethanol, as infusion of the neurotrophic factor in the DMS but not DLS resulted in a reduction of sucrose intake. Together, these findings demonstrate that the BDNF pathway within the DLS controls the level of ethanol self-administration. Importantly, our results suggest that an endogenous signaling pathway within the same brain region that mediates drug-taking behavior also plays a critical role in gating the level of ethanol intake.