产前接触哌醋甲酯会影响大鼠成年期的多巴胺系统和对自然奖励的反应性。
Prenatal exposure to methylphenidate affects the dopamine system and the reactivity to natural reward in adulthood in rats.
作者信息
Lepelletier François-Xavier, Tauber Clovis, Nicolas Céline, Solinas Marcello, Castelnau Pierre, Belzung Catherine, Emond Patrick, Cortese Samuele, Faraone Stephen V, Chalon Sylvie, Galineau Laurent
机构信息
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).
出版信息
Int J Neuropsychopharmacol. 2014 Oct 31;18(4):pyu044. doi: 10.1093/ijnp/pyu044.
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.
背景
哌甲酯（MPH）是治疗儿童注意力缺陷多动障碍（ADHD）的常用药物。然而，将其用于患有ADHD和发作性睡病的成人时，会引发关于孕期接触MPH对大脑有何影响的问题。本研究的目的是使用大鼠模型阐明产前接触MPH的长期神经生物学后果。
方法
我们重点研究了这种治疗对成年多巴胺（DA）系统以及动物对自然奖励的反应性的影响。
结果
本研究表明，产前接触MPH的成年雄性大鼠在DA细胞体和纹状体中，突触前DA标记物的表达升高。我们的结果还表明，经MPH治疗的动物在中脑边缘通路中可能表现出增强的紧张性DA活动，在药物刺激后信噪比改变，以及对可卡因运动效应的反应性降低。最后，我们证明MPH大鼠对蔗糖的偏好和动机降低。
结论
这是第一项临床前研究，报告了产前接触MPH后DA网络的长期神经生物学改变以及自然奖励动机行为的改变。这些结果引发了对孕期MPH治疗可能产生的神经生物学后果的担忧。
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