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

产前接触哌甲酯会影响大鼠的多巴胺系统和成年后对自然奖励的反应

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作者:François-Xavier Lepelletier, Clovis Tauber, Céline Nicolas, Marcello Solinas, Pierre Castelnau, Catherine Belzung, Patrick Emond, Samuele Cortese, Stephen V Faraone, Sylvie Chalon, Laurent Galineau

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.

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.

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.

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