Abstract
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.
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Acknowledgments
This study is supported by the Agence National de la Recherche (ANR-14-CE13-0002-01 ADDiCLOCK JCJC to JM) and the Centre National de la Recherche Scientifique (JM). JHM is supported by TOPGO and Technology Foundation STW, P10-18. We thank Sylviane Gourmelen and Hanan Bouaouda for technical support. Authors declare that they have no conflicts of interest.
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Mendoza, J., van Diepen, H.C., Pereira, R.R. et al. Time-shifting effects of methylphenidate on daily rhythms in the diurnal rodent Arvicanthis ansorgei. Psychopharmacology 235, 2323–2333 (2018). https://doi.org/10.1007/s00213-018-4928-2
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DOI: https://doi.org/10.1007/s00213-018-4928-2