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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Role of calcineurin in nicotine-mediated locomotor sensitization.
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Role of calcineurin in nicotine-mediated locomotor sensitization.

机译：钙调神经磷酸酶在尼古丁介导的运动致敏中的作用。

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摘要

Calcineurin is a serine/threonine phosphatase that contributes to the effects of nicotine on calcium signaling in cultured cortical neurons; however, the role of calcineurin in behavioral responses to nicotine in vivo has not been examined. We therefore determined whether calcineurin blockade could alter nicotine-mediated locomotor sensitization in Sprague Dawley rats using systemic or brain region-specific administration of the calcineurin inhibitors cyclosporine or FK506. Systemic cyclosporine administration decreased calcineurin activity in the brain, attenuated nicotine-mediated locomotor sensitization, and blocked the effects of nicotine on DARPP32 (dopamine- and cAMP-regulated phosphoprotein-32) activation in the striatum. Direct infusion of calcineurin inhibitors cyclosporine or FK506 into the ventral tegmental area (VTA) also attenuated nicotine-mediated locomotor sensitization, whereas infusion of rapamycin, which binds to FK-binding protein but does not inhibit calcineurin, did not affect sensitization. Together, the data suggest that activation of calcineurin, particularly in the VTA, is a novel signaling event important for nicotine-mediated behavior and intracellular signaling.
机译：钙调神经磷酸酶是一种丝氨酸/苏氨酸磷酸酶，有助于烟碱对培养的皮质神经元中钙信号的影响。然而，尚未研究钙调神经磷酸酶在体内对尼古丁的行为反应中的作用。因此，我们使用钙调神经磷酸酶抑制剂环孢霉素或FK506的全身性或脑区特异性给药，确定钙调神经磷酸酶的阻滞是否能改变Sprague Dawley大鼠的尼古丁介导的运动敏化。全身性环孢霉素的施用降低了大脑中钙调神经磷酸酶的活性，减弱了尼古丁介导的运动敏化，并阻断了尼古丁对纹状体中DARPP32（多巴胺和cAMP调节的磷蛋白32）活化的影响。将钙调神经磷酸酶抑制剂环孢菌素或FK506直接输注到腹侧被盖区（VTA）也减弱了尼古丁介导的运动致敏性，而输注与FK结合蛋白结合但不抑制钙调神经磷酸酶的雷帕霉素不影响致敏性。总之，数据表明，钙调神经磷酸酶的激活，特别是在VTA中，是一种新颖的信号传导事件，对尼古丁介导的行为和细胞内信号传导很重要。

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