Glial modulators as potential treatments of psychostimulant abuse.
Glial modulators as potential treatments of psychostimulant abuse.
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DOI：
10.1016/b978-0-12-420118-7.00001-9
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Hauser, Kurt F
中科院分区：
文献类型：
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作者：
Beardsley, Patrick M;Hauser, Kurt F
神经胶质细胞（包括星形胶质细胞、小胶质细胞和少突胶质细胞），构成大脑中的大部分细胞。具有许多与神经元相同的受体，分泌神经递质以及神经营养因子和神经炎症因子，控制神经递质从突触间隙的清除，并与突触可塑性密切相关。尽管它们很普遍且功能广泛，但自 1800 年代中期它们被识别以来，对其潜在的普遍重要性的认识一直难以捉摸，直到最近它们才获得应有的尊重。人们越来越认识到滥用药物（包括精神兴奋剂）会影响神经胶质细胞的活动，而神经胶质细胞的活动又被发现可以调节精神兴奋剂的作用，从而促进了这种认识的发展。这种不断发展的意识已经开始阐明治疗精神兴奋剂滥用的新药物治疗目标，针对这些目标，针对更传统的神经元目标尚未产生单一的、经批准的药物。在本章中，我们讨论神经胶质细胞的分子药理学、生理学和功能关系，特别是考虑到它们作为治疗精神兴奋剂滥用障碍的药物治疗靶点。然后，我们回顾了一系列临床前研究，这些研究操纵了神经胶质细胞的过程，其行为效应支持将神经胶质细胞视为精神兴奋剂滥用药物的药物靶标。然后，我们对治疗精神兴奋剂滥用的相关化合物的当前临床评估以及未来前景的可能性进行评论。
Glia (including astrocytes, microglia and oligodendrocytes), which constitute the majority of cells in the brain. have many of the same receptors as neurons, secrete neurotransmitters and neurotrophic and neuroinflammatory factors, control clearance of neurotransmitters from synaptic clefts, and are intimately involved in synaptic plasticity. Despite their prevalence and spectrum of functions, appreciation of their potential general importance has been elusive since their identification in the mid-1800s, and only relatively recently have they been gaining their due respect. This development of appreciation has been nurtured by the growing awareness that drugs of abuse, including the psychostimulants, affect glial activity, and glial activity, in turn, has been found to modulate the effects of the psychostimulants. This developing awareness has begun to illuminate novel pharmacotherapeutic targets for treating psychostimulant abuse, for which targeting more conventional neuronal targets has not yet resulted in a single, approved medication. In this chapter, we discuss the molecular pharmacology, physiology and functional relationships that the glia have especially in the light in which they present themselves as targets for pharmacotherapeutics intended to treat psychostimulant abuse disorders. We then review a cross section of preclinical studies that have manipulated glial processes whose behavioral effects have been supportive of considering the glia as drug targets for psychostimulant-abuse medications. We then close with comments regarding the current clinical evaluation of relevant compounds for treating psychostimulant abuse, as well as the likelihood of future prospects.