A review of psychostimulant-induced neuroadaptation in developing animals  

动物发育过程中施予精神兴奋剂引起的神经系统适应性(英文)

作　　者：Normand Carrey Michael Wilkinson 

机构地区：[1]IWK健康中心 [2]达尔豪斯大学医学院生理学与生物物理学系

出　　处：《Neuroscience Bulletin》2011年第3期197-214,共18页神经科学通报（英文版）

基　　金：supported by the IWK Health Centre, Nova Scotia Heath Research Foundation (NSHRF), Canadian Institute of Health Research (CIHR), the Atlee Endowment and NRC-Marine Biosciences

摘　　要：The effects of clinically relevant doses of commonly prescribed stimulants methylphenidate （MPH）, d-am- phetamine （d-AMPH）, and dl-AMPH or mixed amphetamine salts （MAS） such as Adderall, on short- and long-term gene neuroadaptations in developing animals have not been widely investigated. In the present review, the effects of oral stimulant administration were compared with those of the subcutaneous or intra-peritoneal route. A selective set of stud- ies between 1979 and 2010, which incorporated in their design developmental period, clinically relevant doses of stimu- lants, and repeated daily doses were reviewed. These studies indicate that neuroadaptation to chronic stimulants includes blunting of stimulated immediate early gene expression, sensitivity of younger （prepubertal） brain to smaller dosages of stimulants, and the persistence of some effects, especially behavioral neuroadaptations, into adulthood. In addition, oral amphetamines （MAS） have more profound effects than does oral MPH. Further animal developmental studies are required to understand potential long-term neuroadaptations to low, daily oral doses of stimulants. Implications for clinical practice were also discussed.临床相关剂量的处方精神兴奋剂,如苯哌啶醋酸甲酯(methylphenidate,MPH)、右旋/左旋苯丙胺和苯丙胺混合盐制剂(如Adderall),对动物特别是发育期动物的长、短期神经系统适应性变化的影响已被广泛研究。本文对精神兴奋剂口服给药途径与皮下和腹腔注射途径的效应进行了比较,并对1979–2010年间的一系列研究进行了综述。这些研究大都在动物不同的发育阶段进行,给予药物的剂量与临床剂量相似,每天给药一次重复多天。研究结果都表明,在兴奋药慢性作用下产生的神经适应性变化包括早期快反应基因(immediate early gene,IEG)表达的减弱、较年轻大脑(青春期前大脑)对更低剂量兴奋药的敏感性以及某些效应一直持续至成人期。要了解每天口服低剂量的精神兴奋剂引起的长期神经适应性改变,还需要更多更进一步的动物实验。此外,兴奋性药物导致的神经系统适应性改变在临床实践中值得借鉴。

关 键 词：PSYCHOSTIMULANTS animal development gene expression enduring effects 

分 类 号：R96[医药卫生—药理学]