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Psychopharmacology (Berl). 2018 Aug;235(8):2323-2333. doi: 10.1007/s00213-018-4928-2. Epub 2018 May 18.

Time-shifting effects of methylphenidate on daily rhythms in the diurnal rodent Arvicanthis ansorgei.

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Institute of Cellular and Integrative Neurosciences, CNRS UPR-3212, University of Strasbourg, 5 rue Blaise Pascal, 67084, Strasbourg, France.
Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands.
Medical Center Kinderplein, Rotterdam, The Netherlands.


People suffering of attention-deficit/hyperactivity disorder (ADHD) and treated with the psychostimulant methylphenidate (MPH) show sleep-wake cycle and daily rhythm alterations despite the beneficial effects of MPH on behavioral symptoms (i.e., hyperactivity, attention). In nocturnal rodents (i.e., mice), chronic exposure to MPH alters the neural activity of the circadian clock in the suprachiasmatic nucleus (SCN), behavioral rhythms, and the sleep-wake cycle. Here, we studied the effects of MPH on daily rhythms of behavior and body temperature of the diurnal rodent Arvicanthis ansorgei. Under a light-dark cycle, chronic exposure to MPH in drinking water delayed the onset of both activity and body temperature rhythms. Interestingly, delays were larger when MPH access was restricted to the first 6 h of the light phase (i.e., activity phase) of the 24-h cycle. Since MPH effects are dependent on animal's fluid intake, in a last experiment, we controlled the time and dose of MPH delivery in Arvicanthis using an intraperitoneal perfusion method. Similarly to the experiment with MPH in drinking water, Arvicanthis showed a delay in the onset of general activity and body temperature when MPH infusions, but not vehicle, were during the first 6 h of the light phase. This study indicates that MPH alters daily rhythms in a time-dependent manner and proposes the use of a diurnal rodent for the study of the effects of MPH on the circadian clock. Knowing the circadian modulation on the effects of MPH in behavior could give new insights in the treatment of ADHD.


ADHD; Arvicanthis; Circadian; Diurnal; Methylphenidate; Suprachiasmatic


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