Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, United States.
Med Hypotheses. 2013 Dec;81(6):988-94. doi: 10.1016/j.mehy.2013.09.009. Epub 2013 Sep 17.
Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug for juveniles and adolescents. Used to treat attention-deficit/hyperactivity disorder (ADHD) and for cognitive enhancement in healthy individuals, it has been regarded as a relatively safe medication for the past several decades. However, a thorough review of the literature reveals that the age-dependent activities of the drug, as well as potential developmental effects, are largely ignored. In addition, the diagnosis of ADHD is subjective, leaving open the possibility of misdiagnosis and excessive prescription of the drug. Recent studies have suggested that early life exposure of healthy rodent models to methylphenidate resulted in altered sleep/wake cycle, heightened stress reactivity, and, in fact, a dosage previously thought of as therapeutic depressed neuronal function in juvenile rats. Furthermore, juvenile rats exposed to low-dose methylphenidate displayed alterations in neural markers of plasticity, indicating that the drug might alter the basic properties of prefrontal cortical circuits. In this review of the current literature, we propose that juvenile exposure to methylphenidate may cause abnormal prefrontal function and impaired plasticity in the healthy brain, strengthening the case for developing a more thorough understanding of methylphenidate's actions on the developing, juvenile brain, as well as better diagnostic measures for ADHD.
哌醋甲酯(利他林)是最常用于治疗青少年注意缺陷多动障碍(ADHD)和促进健康个体认知的精神活性药物。在过去的几十年中,它一直被认为是一种相对安全的药物。然而,对文献的全面审查表明,药物的年龄依赖性活性以及潜在的发育影响在很大程度上被忽视了。此外,ADHD 的诊断是主观的,这使得误诊和过度处方药物的可能性增加。最近的研究表明,健康的幼年啮齿动物模型早期接触哌醋甲酯会导致睡眠/觉醒周期改变、应激反应增强,实际上,以前被认为具有治疗作用的剂量会导致幼年大鼠的神经元功能下降。此外,接触低剂量哌醋甲酯的幼年大鼠表现出神经可塑性标记物的改变,这表明该药物可能改变前额皮质回路的基本特性。在对当前文献的综述中,我们提出,幼年时期接触哌醋甲酯可能导致健康大脑的前额叶功能异常和可塑性受损,这加强了需要更深入地了解哌醋甲酯对发育中、幼年大脑的作用,并制定更好的 ADHD 诊断措施的观点。