Methylphenidate leads to disruptions in rest/wake patterns after discontinuation.

IF 3.3 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2025-07-30 DOI:10.1007/s00213-025-06859-y

Carolyn Cueto, Magdalena R Gonzales, Alexandra N Tejada, Kimberly Guerrero Leon, Alexandra Mora, Andrew Cabrera, Leslie R Amodeo

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引用次数: 0

Abstract

Children with attention-deficit/hyperactivity disorder (ADHD) experience more sleep problems than their peers. As stimulant medications, particularly methylphenidate (MPH), are the most common treatment for pediatric ADHD, there has been growing interest in whether such medications contribute to sleep disturbances and the development of sleep disorders later in life. Despite ongoing interest, evidence related to MPH on sleep functioning in children remains mixed. The present study investigated the effects of MPH on 24-hour rest/wake activity patterns and circadian rhythms in adolescent versus adult rats. Male and female Long-Evans rats were administered MPH (1 or 2 mg/kg, i.p.) or control twice daily for 10 days during either adolescence (PD 30-39) or adulthood (PD 80-89). Non-invasive activity monitors, secured to each rat using custom-fitted jackets, were used to assess circadian rhythms and detailed activity patterns over a 24-hour reverse light/dark cycle. Microanalysis of activity patterns were assessed on the last day of MPH treatment, during acute discontinuation, and after 10 days of prolonged discontinuation. Results showed that repeated MPH administration produced dose- and age-specific increases in activity across the light/dark cycle on the last day of treatment. In adults, this was associated with longer and more frequent active episodes during the dark period, and transient increases in fragmented activity during early withdrawal. MPH also impaired rest quality in female rats, reflected by fewer rest episodes and increased fragmentation during the light period. While some of these disruptions persisted immediately after discontinuation, more pronounced impairments in rest quality emerged after 10 days of withdrawal. These findings suggest that while MPH may enhance activity during treatment in an age- and sex-dependent manner, its discontinuation may lead to lasting reductions in sleep quality in both adolescents and adults who are transiently exposed to the psychostimulants.

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哌甲酯在停药后会导致休息/清醒模式的中断。

患有注意力缺陷/多动障碍（ADHD）的儿童比他们的同龄人经历更多的睡眠问题。由于兴奋剂药物，尤其是哌醋甲酯（MPH），是儿童多动症最常见的治疗方法，人们对这些药物是否会导致睡眠障碍和以后生活中睡眠障碍的发展越来越感兴趣。尽管人们对MPH对儿童睡眠功能的影响一直很感兴趣，但相关证据仍然是混杂的。本研究探讨了MPH对青春期和成年大鼠24小时休息/觉醒活动模式和昼夜节律的影响。在青春期（PD 30-39）或成年期（PD 80-89），雄性和雌性Long-Evans大鼠每天两次给予MPH（1或2 mg/kg， i.p.p）或对照组，持续10天。非侵入性活动监测器使用定制的夹克固定在每只大鼠身上，用于评估昼夜节律和24小时反向光/暗周期的详细活动模式。在MPH治疗的最后一天，急性停药期间和延长停药10天后评估活动模式的微观分析。结果表明，在治疗的最后一天，重复的MPH给药产生了剂量和年龄特异性的光/暗周期活性增加。在成人中，这与黑暗期更长、更频繁的活动发作和早期戒断期间碎片性活动的短暂增加有关。MPH还损害了雌性大鼠的休息质量，反映在休息次数减少和光照期碎片化增加。虽然其中一些中断在停药后立即持续，但停药10天后，休息质量出现了更明显的损害。这些发现表明，虽然MPH可能在治疗期间以年龄和性别依赖的方式增强活动，但对于短暂暴露于精神兴奋剂的青少年和成年人，其停药可能导致睡眠质量持续下降。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.