Time-shifting effects of methylphenidate on daily rhythms in the diurnal rodent Arvicanthis ansorgei
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.
KeywordsArvicanthis Diurnal Circadian Suprachiasmatic Methylphenidate ADHD
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.
- Contini V, Rovaris DL, Victor MM, Grevet EH, Rohde LA, Bau CH (2013) Pharmacogenetics of response to methylphenidate in adult patients with attention-deficit/hyperactivity disorder (ADHD): a systematic review. Eur Neuropsychopharmacol 23(6):555–560. https://doi.org/10.1016/j.euroneuro.2012.05.006 CrossRefPubMedGoogle Scholar
- Corkum P, Panton R, Ironside S, Macpherson M, Williams T (2008) Acute impact of immediate release methylphenidate administered three times a day on sleep in children with attention-deficit/hyperactivity disorder. J Pediatr Psychol 33(4):368–379. https://doi.org/10.1093/jpepsy/jsm106 CrossRefPubMedGoogle Scholar
- Dafny N, Yang PB (2006) The role of age, genotype, sex, and route of acute and chronic administration of methylphenidate: a review of its locomotor effects. Brain Res Bull 68(6):393–405. https://doi.org/10.1016/j.brainresbull.2005.10.005 CrossRefPubMedGoogle Scholar
- Hubbard J, Ruppert E, Calvel L, Robin-Choteau L, Gropp CM, Allemann C, Reibel S, Sage-Ciocca D, Bourgin P (2015) Arvicanthis ansorgei, a novel model for the study of sleep and waking in diurnal rodents. Sleep 38(6):979–988. https://doi.org/10.5665/sleep.4754 PubMedPubMedCentralCrossRefGoogle Scholar
- Koda K, Ago Y, Cong Y, Kita Y, Takuma K, Matsuda T (2010) Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice. J Neurochem 114(1):259–270. https://doi.org/10.1111/j.1471-4159.2010.06750.x PubMedCrossRefGoogle Scholar
- Molina-Carballo A, Naranjo-Gomez A, Uberos J, Justicia-Martinez F, Ruiz-Ramos MJ, Cubero-Millan I, Contreras-Chova F, Augustin-Morales MD, Khaldy-Belkadi H, Munoz-Hoyos A (2013) Methylphenidate effects on blood serotonin and melatonin levels may help to synchronise biological rhythms in children with ADHD. J Psychiatr Res 47(3):377–383. https://doi.org/10.1016/j.jpsychires.2012.09.020 CrossRefPubMedGoogle Scholar
- Novakova M, Paclt I, Ptacek R, Kuzelova H, Hajek I, Sumova A (2011) Salivary melatonin rhythm as a marker of the circadian system in healthy children and those with attention-deficit/hyperactivity disorder. Chronobiol Int 28(7):630–637. https://doi.org/10.3109/07420528.2011.596983 CrossRefPubMedGoogle Scholar
- Pitrosky B, Kirsch R, Malan A, Mocaer E, Pevet P (1999) Organization of rat circadian rhythms during daily infusion of melatonin or S20098, a melatonin agonist. Am J Phys 277(3 Pt 2):R812–R828Google Scholar
- Schwartz G, Amor LB, Grizenko N, Lageix P, Baron C, Boivin DB, Joober R (2004) Actigraphic monitoring during sleep of children with ADHD on methylphenidate and placebo. J Am Acad Child Adolesc Psychiatry 43(10):1276–1282. https://doi.org/10.1097/01.chi.0000135802.94090.93 CrossRefPubMedGoogle Scholar
- Soto PL, Wilcox KM, Zhou Y, Kumar A, Ator NA, Riddle MA, Wong DF, Weed MR (2012) Long-term exposure to oral methylphenidate or dl-amphetamine mixture in peri-adolescent rhesus monkeys: effects on physiology, behavior, and dopamine system development. Neuropsychopharmacology 37(12):2566–2579. https://doi.org/10.1038/npp.2012.119 CrossRefPubMedPubMedCentralGoogle Scholar
- Volobouev VT, Ducroz JF, Aniskin VM, Britton-Davidian J, Castiglia R, Dobigny G, Granjon L, Lombard M, Corti M, Sicard B, Capanna E (2002) Chromosomal characterization of Arvicanthis species (Rodentia, Murinae) from western and Central Africa: implications for taxonomy. Cytogenet Genome Res 96(1–4):250–260. https://doi.org/10.1159/000063041 CrossRefPubMedGoogle Scholar
- Welsh DK, Takahashi JS, Kay SA (2010) Suprachiasmatic nucleus: cell autonomy and network properties. Annu Rev Physiol 72:551–577. https://doi.org/10.1146/annurev-physiol-021909-135919 CrossRefPubMedPubMedCentralGoogle Scholar