Daily methylphenidate and atomoxetine treatment impacts on clock gene protein expression in the mouse brain
Abstract
Circadian rhythms are repeating patterns of physiological and other parameters that recur with periods of approximately 24h, and are generated by an endogenous circadian timekeeping mechanism. Such circadian rhythms, and their underlying molecular mechanisms, are known to be altered by a number of central nervous system acting pharmacological compounds, as well as becoming perturbed in a number of common psychiatric and neurological conditions. The psychostimulant methylphenidate and the non-stimulant atomoxetine are used in the pharmacotherapy of attention deficit hyperactivity disorder, a common condition in which circadian rhythms have been reported to be altered. In the present study we have examined the effects of daily methylphenidate or atomoxetine treatment across 7 days on circadian clock gene product expression across numerous brain regions in the male mouse to test the potential impact of such compounds on circadian timing. We report drug, brain region and molecular specific effects of such treatments, including alterations in expression profiles in the suprachiasmatic nucleus, the master circadian pacemaker. These results indicate that drugs used in the clinical management of attention deficit hyperactivity disorder can alter molecular factors that are believed to underpin circadian timekeeping, and such effects may be of importance in both the therapeutic and side effect profiles of such drugs.
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Another study that assessed the impact of MPH on CLOCK gene protein expression showed that MPH increased c-Fos expression.
“Another study that assessed the impact of MPH on CLOCK gene protein expression showed that MPH increased c-Fos expression.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [210]
MPH increases c-FOS level in a study that assessed the impact of MPH on circadian rhythm and c-FOS expression in the medial septum.
“However, it has also been described that MPH increases c-FOS level in a study that assessed the impact of MPH on circadian rhythm [210] and c-FOS expression in the medial septum (area intimately connected to the hippocampus) [222].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [210]
MPH causes a widespread increase in neuronal activation throughout the cerebral cortex.
“Although the authors did not consider its influence on the circadian functioning of the cerebral cortex, MPH causes a widespread increase in neuronal activation throughout the region [210].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [210]
Animal studies indicate that stimulant and non-stimulant medications can impact circadian processes.
“Animal studies indicate that stimulant and non-stimulant medications can impact on circadian processes (e.g. Antle et al. 2012; Baird et al. 2013; O'Keeffe et al. 2012).”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Baird et al. 2013
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Research works printed but not linked: 4
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“Although the authors did not consider its influence on the circadian functioning of the cerebral cortex, MPH causes a widespread increase in neuronal activation throughout the region [210].”
BackgroundPalm, D., Uzoni, A., Simon, F., Fischer, M., Coogan, A., Tucha, O., Thome, J., & Faltraco, F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.06.007 · Cited by 20 · see citing works
Self-citationGüleç, A., Güler, H. A., & Türkoğlu, S. (2024) · Chronobiology International · doi:10.1080/07420528.2024.2319218 · Cited by 3 · see citing works
- Authors
- Baird, A. L., Coogan, A. N., Kaufling, J., Barrot, M., & Thome, J.
- Affiliations
- Swansea University (GB)
- National University of Ireland, Maynooth (IE)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Coogan, Andrew N.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 1513
- Pages
- 61-71
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2097573847
- Cited by
- 46
- References
- 52
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 5 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 2
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Maynooth University ePrints and eTheses Archive (Maynooth University) (acceptedVersion)
- Funders
- ALB
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- methylphenidate, atomoxetine, clock genes, circadian rhythm, attention deficit hyperactivity disorder, suprachiasmatic nucleus, psychostimulants, brain regions
- MeSH terms
- Atomoxetine Hydrochloride, Central Nervous System Stimulants, Analysis of Variance, Animals, Brain, Circadian Rhythm, Gene Expression Regulation, Male, Methylphenidate, Mice, Inbred C57BL, Propylamines, Proto-Oncogene Proteins c-fos, Mice, CLOCK Proteins, Neuroimaging
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