伏隔核 SK 通道活性降低会增强戒断期间的酒精觅药行为。
Reduced nucleus accumbens SK channel activity enhances alcohol seeking during abstinence.
机构信息
Ernest Gallo Clinic and Research Center, University of California, San Francisco, San Francisco, CA 94608, USA.
出版信息
Neuron. 2010 Mar 11;65(5):682-94. doi: 10.1016/j.neuron.2010.02.015.
Abstract
The cellular mechanisms underlying pathological alcohol seeking remain poorly understood. Here, we show an enhancement of nucleus accumbens (NAcb) core action potential firing ex vivo after protracted abstinence from alcohol but not sucrose self-administration. Increased firing is associated with reduced small-conductance calcium-activated potassium channel (SK) currents and decreased SK3 but not SK2 subunit protein expression. Furthermore, SK activation ex vivo produces greater firing suppression in NAcb core neurons from alcohol- versus sucrose-abstinent rats. Accordingly, SK activation in the NAcb core significantly reduces alcohol but not sucrose seeking after abstinence. In contrast, NAcb shell and lateral dorsal striatal firing ex vivo are not altered after abstinence from alcohol, and SK activation in these regions has little effect on alcohol seeking. Thus, decreased NAcb core SK currents and increased excitability represents a critical mechanism that facilitates motivation to seek alcohol after abstinence.
摘要
病理性酒精觅药的细胞机制仍知之甚少。在这里，我们发现在长期戒酒后，伏隔核（NAcb）核心部位的动作电位放电会增强，但酒精自我给药而不是蔗糖自我给药则不会。放电增加与小电导钙激活钾通道（SK）电流减少和 SK3 亚基蛋白表达减少有关，但 SK2 亚基蛋白表达不变。此外，在体外，SK 的激活会产生更大的抑制作用，使来自酒精而非蔗糖戒断大鼠的 NAcb 核心神经元放电。因此，NAcb 核心部位的 SK 激活在戒酒后会显著减少对酒精的觅药行为，但对蔗糖的觅药行为影响不大。相比之下，NAcb 壳核和外侧背侧纹状体在戒酒后体外的放电并没有改变，而这些区域的 SK 激活对酒精觅药行为几乎没有影响。因此，NAcb 核心部位 SK 电流的减少和兴奋性的增加代表了一种促进酒精觅药的关键机制。
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