Methylphenidate treatment induces oxidative stress in young rat brain
Abstract
Methylphenidate (MPH) is frequently prescribed for the treatment of attention deficit/hyperactivity disorder. Psychostimulants can cause long-lasting neurochemical and behavioral adaptations. Here, we evaluated oxidative damage in the rat brain and the differential age-dependent response to MPH after acute and chronic exposure. We investigated the oxidative damage, assessed by the thiobarbituric acid reactive species (TBARS), and the protein carbonyl assays in cerebellum, prefrontal cortex, hippocampus, striatum, and cerebral cortex of young (25 days old) and adult (60 days old) male Wistar rats after acute and chronic exposure to MPH. Chronic MPH-treated young rats presented a dose-dependent increase in TBARS content and protein carbonyls formation in specific rat brain regions. In the acute exposure, only MPH highest dose increased lipid peroxidation in the hippocampus. No difference in protein carbonylation was observed among groups in all structures analyzed. In adult rats, we did not find oxidative damage in both acute and chronic treatment. Chronic exposure to MPH in induces oxidative damage in young rat brain, differentially from chronic exposure during adulthood. These findings highlight the need for further research to improve understanding of MPH effects on developing nervous system and the potential consequences in adulthood resulting from early-life drug exposure.
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Several studies have shown that MPH modulates oxidative stress in the brain, either increasing or reducing reactive oxygen species (ROS) depending on age, drug dose and brain region, and relate that to neural viability.
“Several studies have shown that MPH modulates oxidative stress in the brain [223, 224], either increasing or reducing reactive oxygen species (ROS) depending on age, drug dose and brain region, and relate that to neural viability.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [224]
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Altered responsiveness to cocaine in rats exposed to methylphenidate during development
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Role of Oxidative Stress and Neuroinflammation in Attention-Deficit/Hyperactivity Disorder
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“Oxidative Stress Several studies have shown that MPH modulates oxidative stress in the brain [223, 224], either increasing or reducing reactive oxygen species (ROS) depending on age, drug dose and brain region, and relate that to neural viability.”
BackgroundJezierski, G., Zehle, S., Bock, J., Braun, K., & Gruss, M. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04927.x · Cited by 41 · see citing works
Schmitz, F., Pierozan, P., Rodrigues, A. F., Biasibetti, H., Grings, M., Zanotto, B., Coelho, D. M., Vargas, C. R., Leipnitz, G., & Wyse, A. T. S. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-0289-1 · Cited by 35 · see citing works
- Authors
- Martins, M. R., Reinke, A., Petronilho, F. C., Gomes, K. M., Dal-Pizzol, F., & Quevedo, J.
- Affiliations
- Universidade do Extremo Sul Catarinense (BR)
- Corresponding author
- Quevedo, João
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 1078
- Issue
- 1
- Pages
- 189-197
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2049263381
- Cited by
- 105
- References
- 8
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 3 · 2020: 8 · 2019: 5 · 2018: 1 · 2017: 9 · 2016: 12 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 6
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina
- Universidade do Extremo Sul Catarinense
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Instituto Mente e Cérebro - Neurociência
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- methylphenidate, oxidative stress, lipid peroxidation, protein carbonylation, psychostimulants, attention deficit hyperactivity disorder, chronic drug exposure, acute drug exposure, hippocampus, cerebellum, prefrontal cortex, striatum, cerebral cortex, developing nervous system
- MeSH terms
- Age Factors, Central Nervous System Stimulants, Analysis of Variance, Animals, Animals, Newborn, Brain, Brain Chemistry, Dose-Response Relationship, Drug, Drug Administration Schedule, Male, Methylphenidate, Rats, Wistar, Thiobarbituric Acid Reactive Substances, Oxidative Stress, Protein Carbonylation, Rats
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