Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects.
Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects.
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DOI：
10.1016/bs.pmbts.2015.10.017
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发表时间：
2016
影响因子：
--
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Sun WL;Quizon PM;Zhu J
精神兴奋剂成瘾被认为是一种慢性精神疾病，其特征是渴望和强迫性寻求和使用药物。在过去的二十年中，越来越多的证据表明，反复接触药物会导致持久的神经化学和细胞变化，从而导致大脑回路中持久的神经适应，并成为强迫性药物消耗和复发的基础。通过细胞间信号级联，滥用药物会诱导奖赏回路的重塑，从而有助于与成瘾相关的学习和记忆的神经可塑性。在这里，我们回顾了细胞外信号调节激酶（ERK）（丝裂原激活蛋白激酶的成员）及其相关的细胞内信号通路在药物诱导的神经适应性变化中的作用，这些神经适应性变化与药物介导的精神运动活动、奖励特性和药物寻求行为的复发相关。我们还讨论了药物和遗传干扰 ERK 相关分子级联反应对滥用物质的神经生物学和行为影响。了解 ERK 信号对药物的动态调节可能为药物成瘾的治疗策略提供新的分子靶点。
Addiction to psychostimulants has been considered as a chronic psychiatric disorder, characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that results in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction.