Persistent Cocaine-Induced Reversal Learning Deficits Are Associated with Altered Limbic Cortico-Striatal Local Field Potential Synchronization
Persistent Cocaine-Induced Reversal Learning Deficits Are Associated with Altered Limbic Cortico-Striatal Local Field Potential Synchronization
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DOI：
10.1523/jneurosci.1440-13.2013
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发表时间：
2013-10-30
影响因子：
5.3
通讯作者：
Grace, Anthony A.
中科院分区：
文献类型：
--
作者：
McCracken, Clinton B.;Grace, Anthony A.
众所周知，反复接触可卡因会导致行为灵活性的持续缺陷。有证据表明，这些缺陷部分是由涉及内侧前额叶和眶额叶皮质（PFC和OFC）、伏隔核（NAC）和基底外侧杏仁核（BLA）的回路介导的。为了评估可卡因对这一回路的影响，我们每天给大鼠服用可卡因14天，然后禁欲4周。然后对动物进行基于交叉迷宫的逆转学习和设置转移任务测试，之后对它们进行麻醉，以便在急性BLA刺激引起的活动之外，同时记录所有四个区域的自发局部场电位（LFP）活动。可卡因治疗（COC）的动物表现出特定的逆转学习缺陷；此外，与盐处理（SAL）大鼠相比，各区域LFP自发振荡功率降低，bla诱导的振荡功率增加。在COC/SAL组无差异的情况下，多巴胺刺激增强了各区域的诱发反应，可卡因刺激降低了自发振荡功率和诱发反应幅度。值得注意的是，可卡因挑战在COC组和SAL组中产生了OFC-BLA、BLA-NAC和OFC-NAC之间一致性的差异变化。这些数据表明，反复暴露于可卡因可以产生沿边缘皮质-纹状体回路的LFP振荡同步的变化，这种变化会持续很长时间直至戒断。此外，这些变化的区域特异性与观察到的行为缺陷密切相关。区域内部和区域之间的异常同步以及随之而来的与执行控制有关的神经回路失调可能导致可卡因滥用者长期的不适应决策。
Repeated exposure to cocaine is known to produce persistent deficits in behavioral flexibility. Evidence suggests that these deficits are mediated in part by a circuit involving the medial prefrontal and orbitofrontal cortices (PFC and OFC), nucleus accumbens (NAC), and basolateral amygdala (BLA). To assess the effects of cocaine on this circuit, we treated rats with cocaine daily for 14 d, followed by 4 weeks of abstinence. Animals were then testedona cross-maze-based reversal learning and set-shifting task, after which they were anesthetized to allow for recording of spontaneous local field potential (LFP) activity simultaneously from all four regions, in addition to activity evoked from acute BLA stimulation. Cocaine-treated (COC) animals showed specific deficits in reversal learning; furthermore, spontaneous LFP oscillation power was reduced and BLA-induced oscillation power was increased in all regions compared with saline-treated (SAL) rats. Theta-burst stimulation of BLA potentiated BLA-evoked responses in all regions and cocaine challenge reduced spontaneous oscillation power and evoked response amplitude, with no COC/SAL group differences. Notably, cocaine challenge produced differential changes in coherence between OFC-BLA, BLA-NAC, and OFC-NAC in COC and SAL groups. These data indicate that repeated exposure to cocaine can produce changes in oscillatory LFP synchronization along limbic cortico-striatal circuits that persist long into abstinence. Furthermore, the regional specificity of these changes strongly correlates with the observed behavioral deficits. Aberrant synchronization within and between regions and consequent dysregulation of the neurocircuitry involved in executive control may contribute to the long-lasting maladaptive decision making seen in cocaine abusers.