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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >A single infusion of brain-derived neurotrophic factor into the ventral tegmental area induces long-lasting potentiation of cocaine seeking after withdrawal.
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A single infusion of brain-derived neurotrophic factor into the ventral tegmental area induces long-lasting potentiation of cocaine seeking after withdrawal.

机译：将脑源性神经营养因子单次注入腹侧被盖区可诱导戒断后寻求可卡因的持久作用。

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摘要

Cocaine addiction in humans is associated with long-term propensity to relapse. Using a rat relapse model, we found that cocaine seeking induced by exposure to cocaine-associated cues progressively increases after withdrawal. This progressive increase is associated with increases in brain-derived nerve growth factor (BDNF) levels within the mesolimbic dopamine system. Based on these findings, we studied whether BDNF infusions into the ventral tegmental area (VTA), the cell body region of mesolimbic dopamine neurons, would potentiate cocaine seeking after withdrawal. Rats were trained to self-administer cocaine for 10 d, and cocaine seeking was measured in extinction tests 3, 10, or 30 d after withdrawal. During testing, rats were exposed to contextual cues that had predicted cocaine availability during training, and lever presses resulted in contingent presentations of a discrete tone-light cue that was previously temporally paired with cocaine infusions. BDNF (0-0.75 microg/site) or nerve growth factor (NGF; 0-0.75 microg/site) was infused into the VTA 1-2 hr after the last self-administration session. To examine the role of the mitogen-activated protein kinase (MAPK) pathway in BDNF effects, U0126 (1 microg/site), an MEK inhibitor, was used. A single intra-VTA infusion of BDNF, but not NGF, induced long-lasting enhancement of cocaine seeking for up to 30 d, an effect reversed by U0126. In contrast, neither BDNF infusions into the substantia nigra, nor acute intra-VTA BDNF infusions 2 hr before testing on day 3 of withdrawal, were effective. These data suggest that BDNF-mediated neuroadaptations in mesolimbic areas are involved in the persistent cocaine seeking induced by exposure to drug cues after withdrawal.
机译：人类的可卡因成瘾与长期复发的倾向有关。使用大鼠复发模型，我们发现戒断后因暴露于可卡因相关提示而诱导的可卡因搜寻逐渐增加。这种进行性增加与中脑边缘多巴胺系统中脑源性神经生长因子（BDNF）水平的增加有关。基于这些发现，我们研究了将BDNF输注到腹侧被盖区（VTA）（中脑边缘多巴胺神经元的细胞体区域）是否会增强戒断后的可卡因寻找作用。训练大鼠自我给药可卡因10 d，并在戒断后3、10或30 d的消光试验中测定可卡因的寻找。在测试过程中，大鼠暴露于可以预测训练期间可卡因可利用性的上下文线索，而杠杆按压会导致离散音调提示的可能出现，该提示以前在时间上与可卡因输注配对。在最后一次自我给药后1-2小时，将BDNF（0-0.75微克/位）或神经生长因子（NGF; 0-0.75微克/位）注入VTA。为了检查有丝分裂原激活的蛋白激酶（MAPK）通路在BDNF效应中的作用，使用了MEK抑制剂U0126（1微克/位）。 VTA内单次注入BDNF而不是NGF诱导可卡因的持久增强作用，持续长达30 d，U0126逆转了这一作用。相反，在退出第3天进行测试前2小时，向黑质中注入BDNF或在VTA内进行急性BDNF急性输注均无效。这些数据表明中脑边缘区域中BDNF介导的神经适应与戒断后暴露于药物提示诱导的持续可卡因搜寻有关。

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