College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute and Department of Psychiatry, Division on Substance Abuse, 1051 Riverside Drive, New York, NY 10032, USA.
Expert Opin Investig Drugs. 2012 Feb;21(2):169-78. doi: 10.1517/13543784.2012.651123. Epub 2012 Jan 11.
Commonly abused drugs including opioids, stimulants and alcohol activate glia cells, an effect that has been identified across species. Glia, specifically astrocytes and microglia, have been shown to contribute directly to behaviors predictive of the abuse liability of these drugs. Although still in its infancy, research investigating the effects of pharmacological modulation of glial activity on these behaviors has provided encouraging findings suggesting glial cell modulators as potential pharmacotherapies for substance-use disorders.
This review first explores the evidence establishing glial-mediated modulations of behaviors associated with opioid, stimulant and alcohol exposure, with emphasis placed on the neuroanatomical substrates for these effects. Next, neurobiological and behavioral studies evaluating the ability of glial cell modulators to prevent and reverse the effects of these abused substances will be considered. Finally, the potential clinical efficacy of glial cell modulators as a novel pharmacological approach to treat substance-use disorders in relation to currently available, conventional pharmacotherapies will be discussed.
Though the relationship between drug-induced glial activity and behaviors indicative of drug abuse and dependence is not yet fully elucidated, the evidence for the association continues to grow. The use of glial modulators as pharmacological tools to investigate this relationship has also yielded findings supporting their potential clinical efficacy for treating substance-use disorders.
阿片类药物、兴奋剂和酒精等常见滥用药物会激活神经胶质细胞,这一效应在不同物种中都已得到证实。神经胶质细胞,特别是星形胶质细胞和小胶质细胞,已被证明直接参与预测这些药物滥用倾向的行为。尽管研究仍处于起步阶段,但研究药物调节神经胶质细胞活性对这些行为的影响已经提供了令人鼓舞的发现,表明神经胶质细胞调节剂可能是治疗物质使用障碍的潜在药物。
这篇综述首先探讨了证据,证明了神经胶质细胞介导的与阿片类药物、兴奋剂和酒精暴露相关行为的调节,重点是这些作用的神经解剖学基础。接下来,将考虑评估神经胶质细胞调节剂预防和逆转这些滥用物质作用的神经生物学和行为研究。最后,将讨论神经胶质细胞调节剂作为一种治疗物质使用障碍的新型药理学方法的潜在临床疗效,以及与目前可用的常规药物治疗相比。
尽管药物诱导的神经胶质细胞活性与表明药物滥用和依赖的行为之间的关系尚未完全阐明,但这种关联的证据仍在不断增加。使用神经胶质调节剂作为研究这种关系的药理学工具也产生了支持它们治疗物质使用障碍的潜在临床疗效的发现。