Incubation of nicotine seeking is associated with enhanced protein kinase A-regulated signaling of dopamine- and cAMP-regulated phosphoprotein of 32 kDa in the insular cortex.
Incubation of nicotine seeking is associated with enhanced protein kinase A-regulated signaling of dopamine- and cAMP-regulated phosphoprotein of 32 kDa in the insular cortex.
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寻求尼古丁的孵育与增强的蛋白激酶A调节的蛋白激酶A调节的多巴胺和cAMP调节的磷酸蛋白在岛状皮质中的磷酸蛋白的信号传导有关。
DOI：
10.1111/j.1460-9568.2010.07114.x
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发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
Lynch WJ
中科院分区：
文献类型：
--
作者：
Abdolahi A;Acosta G;Breslin FJ;Hemby SE;Lynch WJ
一项近期的临床研究表明，岛叶皮质受损会扰乱烟草成瘾。这种效应的神经生物学机制尚未被了解。在这项研究中，我们使用尼古丁成瘾的动物模型来检验岛叶皮质中多巴胺（DA）和环磷腺苷酸调节的32 kDa磷蛋白（DARPP - 32）水平的变化是否可能与尼古丁成瘾易感性的变化有关。DARPP - 32是一种富含含多巴胺D1受体的多巴胺神经元的磷蛋白。一旦大鼠学会自行给药，它们每天可无限制地获取尼古丁（0.01毫克/千克/次注射），每天23小时，共10天。每次注射都伴有视觉提示（刺激光）和听觉提示（泵的声音）。在两种不同的戒断间隔（1天和7天），分别对不同组的大鼠进行了线索诱导的复吸范式下的尼古丁寻求行为评估以及使用蛋白质印迹分析评估的DARPP - 32信号标志物检测。与其他滥用药物的研究结果一致，与1天戒断复吸组的大鼠相比，7天戒断组的大鼠在消退行为上花费的时间更长，并且在复吸测试期间反应水平更高。相对于生理盐水对照组，7天戒断组而非1天戒断组的大鼠在岛叶皮质的蛋白激酶A位点磷酸化的DARPP - 32水平更高。这些结果表明，在长时间可自行获取尼古丁之后会出现药物寻求行为的潜伏现象，并表明通过DARPP - 32在苏氨酸34位点的磷酸化增强岛叶皮质中的蛋白激酶A信号与这种效应有关。
A recent clinical study demonstrated that damage to the insular cortex can disrupt tobacco addiction. The neurobiological mechanisms for this effect are not yet understood. In this study we used an animal model of nicotine addiction to examine the possibility that changes in insular cortex levels of dopamine (DA)- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), a phosphoprotein enriched in DA neurons containing DA D1 receptors, may be associated with changes in vulnerability to nicotine addiction. Once rats acquired self-administration, they were given unlimited access to nicotine (0.01 mg/kg/infusion) for 23 h/day for a total of 10 days. Each infusion was paired with a visual cue (stimulus light) and auditory cue (sound of pump). Nicotine seeking, as assessed under a cue-induced reinstatement paradigm, and markers of DARPP-32 signaling, as assessed using western blot analysis, were examined in separate groups of rats at two different abstinent intervals: 1 and 7 days. Consistent with findings with other drugs of abuse, rats in the 7-day abstinence group took longer to extinguish and responded at higher levels during reinstatement testing as compared with rats in the 1-day reinstatement group. Relative to saline controls, rats in the 7-day but not the 1-day abstinence group had higher levels of DARPP-32 phosphorylated at the protein kinase A site in the insular cortex. These results demonstrate incubation of drug seeking following extended access to nicotine self-administration and suggest that enhanced protein kinase A signaling in the insular cortex via phosphorylation of DARPP-32 at Thr34 is associated with this effect.
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影响因子：
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作者：
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DOI：
10.1073/pnas.0808023105
发表时间：
2008-12-09
影响因子：
11.1
作者：
Hollander, Jonathan A.;Lu, Qun;Kenny, Paul J.
通讯作者：
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