Addiction-related gene regulation: risks of exposure to cognitive enhancers vs. other psychostimulants.
Addiction-related gene regulation: risks of exposure to cognitive enhancers vs. other psychostimulants.
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DOI：
10.1016/j.pneurobio.2012.10.001
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发表时间：
2013-01
影响因子：
6.7
通讯作者：
Van Waes, Vincent
中科院分区：
文献类型：
--
作者：
Steiner, Heinz;Van Waes, Vincent
关键词：
精神兴奋剂哌甲酯（利他林，Concerta），安非他明（Adderall）和莫达非尼（Provigil）被广泛用于治疗注意力缺陷多动障碍和嗜睡症等疾病，并且越来越多地被健康人用作“认知增强剂”。然而，这些药物的长期神经元效应知之甚少。在过去的20年里，大量的研究调查了可卡因和安非他明等精神兴奋剂对大脑基因调控的影响，因为这些分子变化被认为是精神兴奋剂成瘾的关键。这项工作已经确定了一些详细的神经化学和细胞机制，介导精神兴奋剂诱导的基因调控，也确定了这些药物改变的神经系统。受影响最严重的大脑系统是皮质纹状体回路，它是皮质-基底神经节-皮质回路的一部分，调节动机行为。对这种基因调控至关重要的神经递质是与谷氨酸相互作用的多巴胺，而其他神经递质（例如，5-羟色胺）起调节作用。本文综述了（1）可卡因和安非他明诱导的皮质纹状体回路基因调控的主要研究结果，试图为（2）哌甲酯，医用安非他明（Adderall）和莫达非尼产生的分子变化的评估提供细胞框架。研究结果得出的结论是，长期接触这些认知增强剂可以诱导皮质纹状体回路中的基因调节效应，这种效应在性质上与可卡因和其他安非他明的效应相似。这些神经元的变化可能有助于精神兴奋剂认知增强剂的成瘾倾向。
The psychostimulants methylphenidate (Ritalin, Concerta), amphetamine (Adderall), and modafinil (Provigil) are widely used in the treatment of medical conditions such as attention-deficit hyperactivity disorder and narcolepsy and, increasingly, as “cognitive enhancers” by healthy people. The long-term neuronal effects of these drugs, however, are poorly understood. A substantial amount of research over the past 2 decades has investigated the effects of psychostimulants such as cocaine and amphetamines on gene regulation in the brain because these molecular changes are considered critical for psychostimulant addiction. This work has determined in some detail the neurochemical and cellular mechanisms that mediate psychostimulant-induced gene regulation and has also identified the neuronal systems altered by these drugs. Among the most affected brain systems are corticostriatal circuits, which are part of cortico-basal ganglia-cortical loops that mediate motivated behavior. The neurotransmitters critical for such gene regulation are dopamine in interaction with glutamate, while other neurotransmitters (e.g., serotonin) play modulatory roles. This review presents (1) an overview of the main findings on cocaine- and amphetamine-induced gene regulation in corticostriatal circuits in an effort to provide a cellular framework for (2) an assessment of the molecular changes produced by methylphenidate, medical amphetamine (Adderall), and modafinil. The findings lead to the conclusion that protracted exposure to these cognitive enhancers can induce gene regulation effects in corticostriatal circuits that are qualitatively similar to those of cocaine and other amphetamines. These neuronal changes may contribute to the addiction liability of the psychostimulant cognitive enhancers.
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影响因子：
2.7
作者：
Badiani, A;Oates, MM;Robinson, TE
通讯作者：
Robinson, TE
影响因子：
11
作者：
Berman, S. M.;Kuczenski, R.;McCracken, J. T.;London, E. D.
通讯作者：
London, E. D.
影响因子：
3.4
作者：
Banerjee, Partha S.;Aston, James;Zetterstroem, Tyra S. C.
通讯作者：
Zetterstroem, Tyra S. C.
影响因子：
6.1
作者：
Andersson, M;Hilbertson, A;Cenci, MA
通讯作者：
Cenci, MA
影响因子：
3.4
作者：
Andersson, M;Westin, JE;Cenci, MA
通讯作者：
Cenci, MA