Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Department of Pharmacology and Toxicology, Clinical Research Institute on Addictions, Jacobs School of Medicine and Biomedical Sciences, State University at Buffalo, Buffalo, New York.
Department of Nuclear Medicine, State University of New York at Buffalo, Buffalo, New York, USA.
Synapse. 2022 Aug;76(9-10):17-30. doi: 10.1002/syn.22243. Epub 2022 Jun 30.
Methylphenidate (MP) is a psychostimulant chronically prescribed for the treatment of attention deficit hyperactivity disorder (ADHD). Additionally, MP users may take breaks from using the medication during "drug holidays," which may include short-term or long-term breaks from medication. The present study utilized fluorodeoxyglucose (FDG) positron emission tomography (PET) to analyze the effects of chronic oral MP use and abstinence on brain glucose metabolism (BGluM) in rats at two different doses: high dose (HD) and low dose (LD). The schedule of treatment was 3 weeks on-treatment and 1 week off-treatment for a period of 13 weeks, followed by an abstinence period of 4 total weeks. Results showed that chronic MP treatment using this schedule did not lead to significant changes in BGluM when comparing the control to HD MP groups. However, significant activation in BGluM was observed after periods of abstinence between control and HD MP rats in the following brain regions: the trigeminal nucleus, reticular nucleus, inferior olive, lemniscus, mesencephalic reticular formation, inferior colliculus, and several areas of the cerebellum. These brain regions and functional brain circuit play a role in facial sensory function, the auditory pathway, organizing connections between the thalamus and cortex, motor learning, auditory function, control over eye movement, auditory information integration, and both motor and cognitive functions. These results, when considered with previous studies, indicate that MP schedule of use may have differing effects on BGluM. BGluM following long-term MP use was dependent on MP dose and schedule of use in rats. This study was conducted in non-ADHD model rats with the aim to establish an understanding of the effects of MP itself, especially given the growing chronic off-label and prescribed use of MP. Further studies are needed for analysis of the drug's effects on an ADHD model.
哌醋甲酯（MP）是一种长期用于治疗注意力缺陷多动障碍（ADHD）的精神兴奋剂。此外，MP 用户可能会在“药物假期”期间停止使用药物，其中可能包括短期或长期停药。本研究利用氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）分析两种不同剂量（高剂量[HD]和低剂量[LD]）慢性口服 MP 使用和戒断对大鼠脑葡萄糖代谢（BGluM）的影响。治疗方案为 3 周治疗期和 1 周停药期，共 13 周，随后停药 4 周。结果表明，当将对照与 HD-MP 组进行比较时，这种方案的慢性 MP 治疗并未导致 BGluM 发生显著变化。然而，在对照与 HD-MP 大鼠之间的戒断期间，观察到以下脑区的 BGluM 显著激活：三叉神经核、网状核、下橄榄核、薄束、中脑网状结构、下丘和小脑的几个区域。这些脑区和功能脑回路在面部感觉功能、听觉通路、丘脑和皮层之间的连接组织、运动学习、听觉功能、眼球运动控制、听觉信息整合以及运动和认知功能中发挥作用。这些结果与之前的研究一起表明，MP 的使用方案可能对 BGluM 产生不同的影响。长期使用 MP 后，BGluM 取决于 MP 剂量和使用方案。本研究在非 ADHD 模型大鼠中进行，目的是了解 MP 本身的影响，特别是考虑到 MP 的长期非标签和处方使用不断增加。需要进一步的研究来分析药物对 ADHD 模型的影响。
