Abstinence following intermittent methylphenidate exposure dose-dependently modifies brain glucose metabolism in the rat brain,SYNAPSE

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Abstinence following intermittent methylphenidate exposure dose-dependently modifies brain glucose metabolism in the rat brain
SYNAPSE ( IF 1.6 ) Pub Date : 2022-06-21 , DOI: 10.1002/syn.22243
Eliz Arnavut ₁ , John Hamilton ₁ , Rutao Yao ₂ , Munawwar Sajjad ₂ , Michael Hadjiargyrou ₃ , David Komatsu ₄ , Panayotis K Thanos _{1,

5}

Affiliation

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.

中文翻译：

间歇性哌醋甲酯暴露后的禁欲剂量依赖性地改变大鼠脑中的脑葡萄糖代谢

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”期间暂停服药，其中可能包括短期或长期的药物休息。本研究利用氟脱氧葡萄糖 (FDG) 正电子发射断层扫描 (PET) 分析了两种不同剂量：高剂量 (HD) 和低剂量 (LD) 长期口服 MP 和禁欲对大鼠脑葡萄糖代谢 (BGluM) 的影响. 治疗计划是治疗 3 周和停止治疗 1 周，为期 13 周，然后是总共 4 周的禁欲期。结果表明，当将对照组与 HD MP 组进行比较时，使用该方案进行的慢性 MP 治疗不会导致 BGluM 发生显着变化。然而，在对照组和 HD MP 大鼠在以下脑区禁欲一段时间后，观察到 BGluM 的显着激活：三叉核、网状核、下橄榄核、丘系、中脑网状结构、下丘和小脑的几个区域。这些大脑区域和功能性大脑回路在面部感觉功能、听觉通路、丘脑和皮层之间的组织连接、运动学习、听觉功能、对眼球运动的控制、听觉信息整合以及运动和认知功能中发挥作用。这些结果，当考虑到以前的研究时，表明使用 MP 的时间表可能对 BGluM 有不同的影响。长期使用 MP 后的 BGluM 取决于大鼠的 MP 剂量和使用时间表。这项研究是在非 ADHD 模型大鼠中进行的，目的是了解 MP 本身的影响，特别是考虑到越来越多的慢性标签外和规定使用 MP。需要进一步研究来分析药物对 ADHD 模型的影响。

更新日期：2022-06-21

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