Prenatal exposure to methylphenidate affects the dopamine system and the reactivity to natural reward in adulthood in rats.

François-Xavier Lepelletier, Clovis Tauber, Céline Nicolas, Marcello Solinas, Pierre Castelnau, Catherine Belzung, Patrick Emond, Samuele Cortese, Stephen V. Faraone, Sylvie Chalon, Laurent Galineau
International Journal of Neuropsychopharmacology. 2015-01-22; 18(4):
DOI: 10.1093/ijnp/pyu044

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Lepelletier FX(1), Tauber C(1), Nicolas C(1), Solinas M(1), Castelnau P(1),
Belzung C(1), Emond P(1), Cortese S(1), Faraone SV(1), Chalon S(1), Galineau
L(2).

Author information:
(1)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).
(2)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). .

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.