title: Prenatal exposure to methylphenidate affects the dopamine system and the reactivity to natural reward in adulthood in rats.
abstract: BACKGROUND
  Methylphenidate (MPH) is a commonly-used medication for the treatment of children with Attention-Deficit/Hyperactivity Disorders (ADHD). However, its prescription to adults with ADHD and narcolepsy raises the question of how the brain is impacted by MPH exposure during pregnancy. The goal of this study was to elucidate the long-term neurobiological consequences of prenatal exposure to MPH using a rat model.
  
  
  METHODS
  We focused on the effects of such treatment on the adult dopamine (DA) system and on the reactivity of animals to natural rewards.
  
  
  RESULTS
  This study shows that adult male rats prenatally exposed to MPH display elevated expression of presynaptic DA markers in the DA cell bodies and the striatum. Our results also suggest that MPH-treated animals could exhibit increased tonic DA activity in the mesolimbic pathway, altered signal-to-noise ratio after a pharmacological stimulation, and decreased reactivity to the locomotor effects of cocaine. Finally, we demonstrated that MPH rats display a decreased preference and motivation for sucrose.
  
  
  CONCLUSIONS
  This is the first preclinical study reporting long-lasting neurobiological alterations of DA networks as well as alterations in motivational behaviors for natural rewards after a prenatal exposure to MPH. These results raise concerns about the possible neurobiological consequences of MPH treatment during pregnancy.
authors.affiliation: Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR 930, Tours, France (Drs Lepelletier, Tauber, Castelnau, Belzung, Emond, Chalon, and Galineau); Experimental and Clinical Neurosciences Laboratory, INSERM U1084, Poitiers, France (Drs Nicolas and Solinas); University of Poitiers, Poitiers, France (Drs Nicolas and Solinas); Child Neurology Unit, University Hospital, University of Tours, Tours, France (Dr Castelnau); Department of Neurosciences, University François Rabelais of Tours, Tours, France (Drs Belzung and Galineau); Institute for Pediatric Neuroscience, NYU Child Study Center, Langone Medical Center, NY (Dr Cortese); Child Psychiatry Centre, University Hospital, University of Tours, Tours, France (Dr Cortese); Departments of Psychiatry and of Neuroscience and Physiology, Upstate Medical University, State University of New York, Syracuse, NY (Dr Faraone).
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Lepelletier
authors.affiliation: Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR 930, Tours, France (Drs Lepelletier, Tauber, Castelnau, Belzung, Emond, Chalon, and Galineau); Experimental and Clinical Neurosciences Laboratory, INSERM U1084, Poitiers, France (Drs Nicolas and Solinas); University of Poitiers, Poitiers, France (Drs Nicolas and Solinas); Child Neurology Unit, University Hospital, University of Tours, Tours, France (Dr Castelnau); Department of Neurosciences, University François Rabelais of Tours, Tours, France (Drs Belzung and Galineau); Institute for Pediatric Neuroscience, NYU Child Study Center, Langone Medical Center, NY (Dr Cortese); Child Psychiatry Centre, University Hospital, University of Tours, Tours, France (Dr Cortese); Departments of Psychiatry and of Neuroscience and Physiology, Upstate Medical University, State University of New York, Syracuse, NY (Dr Faraone).
authors.forename: Clovis
authors.initials: C
authors.lastname: Tauber
authors.affiliation: Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR 930, Tours, France (Drs Lepelletier, Tauber, Castelnau, Belzung, Emond, Chalon, and Galineau); Experimental and Clinical Neurosciences Laboratory, INSERM U1084, Poitiers, France (Drs Nicolas and Solinas); University of Poitiers, Poitiers, France (Drs Nicolas and Solinas); Child Neurology Unit, University Hospital, University of Tours, Tours, France (Dr Castelnau); Department of Neurosciences, University François Rabelais of Tours, Tours, France (Drs Belzung and Galineau); Institute for Pediatric Neuroscience, NYU Child Study Center, Langone Medical Center, NY (Dr Cortese); Child Psychiatry Centre, University Hospital, University of Tours, Tours, France (Dr Cortese); Departments of Psychiatry and of Neuroscience and Physiology, Upstate Medical University, State University of New York, Syracuse, NY (Dr Faraone).
authors.forename: Céline
authors.initials: C
authors.lastname: Nicolas
authors.affiliation: Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR 930, Tours, France (Drs Lepelletier, Tauber, Castelnau, Belzung, Emond, Chalon, and Galineau); Experimental and Clinical Neurosciences Laboratory, INSERM U1084, Poitiers, France (Drs Nicolas and Solinas); University of Poitiers, Poitiers, France (Drs Nicolas and Solinas); Child Neurology Unit, University Hospital, University of Tours, Tours, France (Dr Castelnau); Department of Neurosciences, University François Rabelais of Tours, Tours, France (Drs Belzung and Galineau); Institute for Pediatric Neuroscience, NYU Child Study Center, Langone Medical Center, NY (Dr Cortese); Child Psychiatry Centre, University Hospital, University of Tours, Tours, France (Dr Cortese); Departments of Psychiatry and of Neuroscience and Physiology, Upstate Medical University, State University of New York, Syracuse, NY (Dr Faraone).
authors.forename: Marcello
authors.initials: M
authors.lastname: Solinas
authors.affiliation: Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR 930, Tours, France (Drs Lepelletier, Tauber, Castelnau, Belzung, Emond, Chalon, and Galineau); Experimental and Clinical Neurosciences Laboratory, INSERM U1084, Poitiers, France (Drs Nicolas and Solinas); University of Poitiers, Poitiers, France (Drs Nicolas and Solinas); Child Neurology Unit, University Hospital, University of Tours, Tours, France (Dr Castelnau); Department of Neurosciences, University François Rabelais of Tours, Tours, France (Drs Belzung and Galineau); Institute for Pediatric Neuroscience, NYU Child Study Center, Langone Medical Center, NY (Dr Cortese); Child Psychiatry Centre, University Hospital, University of Tours, Tours, France (Dr Cortese); Departments of Psychiatry and of Neuroscience and Physiology, Upstate Medical University, State University of New York, Syracuse, NY (Dr Faraone).
authors.forename: Pierre
authors.initials: P
authors.lastname: Castelnau
authors.affiliation: Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR 930, Tours, France (Drs Lepelletier, Tauber, Castelnau, Belzung, Emond, Chalon, and Galineau); Experimental and Clinical Neurosciences Laboratory, INSERM U1084, Poitiers, France (Drs Nicolas and Solinas); University of Poitiers, Poitiers, France (Drs Nicolas and Solinas); Child Neurology Unit, University Hospital, University of Tours, Tours, France (Dr Castelnau); Department of Neurosciences, University François Rabelais of Tours, Tours, France (Drs Belzung and Galineau); Institute for Pediatric Neuroscience, NYU Child Study Center, Langone Medical Center, NY (Dr Cortese); Child Psychiatry Centre, University Hospital, University of Tours, Tours, France (Dr Cortese); Departments of Psychiatry and of Neuroscience and Physiology, Upstate Medical University, State University of New York, Syracuse, NY (Dr Faraone).
authors.forename: Catherine
authors.initials: C
authors.lastname: Belzung
authors.affiliation: Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR 930, Tours, France (Drs Lepelletier, Tauber, Castelnau, Belzung, Emond, Chalon, and Galineau); Experimental and Clinical Neurosciences Laboratory, INSERM U1084, Poitiers, France (Drs Nicolas and Solinas); University of Poitiers, Poitiers, France (Drs Nicolas and Solinas); Child Neurology Unit, University Hospital, University of Tours, Tours, France (Dr Castelnau); Department of Neurosciences, University François Rabelais of Tours, Tours, France (Drs Belzung and Galineau); Institute for Pediatric Neuroscience, NYU Child Study Center, Langone Medical Center, NY (Dr Cortese); Child Psychiatry Centre, University Hospital, University of Tours, Tours, France (Dr Cortese); Departments of Psychiatry and of Neuroscience and Physiology, Upstate Medical University, State University of New York, Syracuse, NY (Dr Faraone).
authors.forename: Patrick
authors.initials: P
authors.lastname: Emond
authors.affiliation: Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR 930, Tours, France (Drs Lepelletier, Tauber, Castelnau, Belzung, Emond, Chalon, and Galineau); Experimental and Clinical Neurosciences Laboratory, INSERM U1084, Poitiers, France (Drs Nicolas and Solinas); University of Poitiers, Poitiers, France (Drs Nicolas and Solinas); Child Neurology Unit, University Hospital, University of Tours, Tours, France (Dr Castelnau); Department of Neurosciences, University François Rabelais of Tours, Tours, France (Drs Belzung and Galineau); Institute for Pediatric Neuroscience, NYU Child Study Center, Langone Medical Center, NY (Dr Cortese); Child Psychiatry Centre, University Hospital, University of Tours, Tours, France (Dr Cortese); Departments of Psychiatry and of Neuroscience and Physiology, Upstate Medical University, State University of New York, Syracuse, NY (Dr Faraone).
authors.forename: Samuele
authors.initials: S
authors.lastname: Cortese
authors.affiliation: Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR 930, Tours, France (Drs Lepelletier, Tauber, Castelnau, Belzung, Emond, Chalon, and Galineau); Experimental and Clinical Neurosciences Laboratory, INSERM U1084, Poitiers, France (Drs Nicolas and Solinas); University of Poitiers, Poitiers, France (Drs Nicolas and Solinas); Child Neurology Unit, University Hospital, University of Tours, Tours, France (Dr Castelnau); Department of Neurosciences, University François Rabelais of Tours, Tours, France (Drs Belzung and Galineau); Institute for Pediatric Neuroscience, NYU Child Study Center, Langone Medical Center, NY (Dr Cortese); Child Psychiatry Centre, University Hospital, University of Tours, Tours, France (Dr Cortese); Departments of Psychiatry and of Neuroscience and Physiology, Upstate Medical University, State University of New York, Syracuse, NY (Dr Faraone).
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.affiliation: Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR 930, Tours, France (Drs Lepelletier, Tauber, Castelnau, Belzung, Emond, Chalon, and Galineau); Experimental and Clinical Neurosciences Laboratory, INSERM U1084, Poitiers, France (Drs Nicolas and Solinas); University of Poitiers, Poitiers, France (Drs Nicolas and Solinas); Child Neurology Unit, University Hospital, University of Tours, Tours, France (Dr Castelnau); Department of Neurosciences, University François Rabelais of Tours, Tours, France (Drs Belzung and Galineau); Institute for Pediatric Neuroscience, NYU Child Study Center, Langone Medical Center, NY (Dr Cortese); Child Psychiatry Centre, University Hospital, University of Tours, Tours, France (Dr Cortese); Departments of Psychiatry and of Neuroscience and Physiology, Upstate Medical University, State University of New York, Syracuse, NY (Dr Faraone).
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chalon
authors.affiliation: Université François-Rabelais de Tours, Inserm, Imagerie et Cerveau UMR 930, Tours, France (Drs Lepelletier, Tauber, Castelnau, Belzung, Emond, Chalon, and Galineau); Experimental and Clinical Neurosciences Laboratory, INSERM U1084, Poitiers, France (Drs Nicolas and Solinas); University of Poitiers, Poitiers, France (Drs Nicolas and Solinas); Child Neurology Unit, University Hospital, University of Tours, Tours, France (Dr Castelnau); Department of Neurosciences, University François Rabelais of Tours, Tours, France (Drs Belzung and Galineau); Institute for Pediatric Neuroscience, NYU Child Study Center, Langone Medical Center, NY (Dr Cortese); Child Psychiatry Centre, University Hospital, University of Tours, Tours, France (Dr Cortese); Departments of Psychiatry and of Neuroscience and Physiology, Upstate Medical University, State University of New York, Syracuse, NY (Dr Faraone). laurent.galineau@univ-tours.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Galineau
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology*; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics / Q000633:toxicity*; D003042:Cocaine / Q000494:pharmacology; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D008774:Methylphenidate / Q000493:pharmacokinetics / Q000633:toxicity*; D009042:Motivation / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012201:Reward
chemical_list: D000697:Central Nervous System Stimulants; D019422:Dietary Sucrose; D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate; D003042:Cocaine; D004298:Dopamine
keywords: dopamine; methylphenidate; motivation; prenatal; rat; sucrose