Bock J, Breuer S, Poeggel G, Braun K
Institute of Biology, Department of Zoology/Developmental Neurobiology, Otto von Guericke University, Leipziger Str. 44, 39118, Magdeburg, Germany.
Center for Behavioral Brain Science, Otto von Guericke University Magdeburg, Magdeburg, Germany.
Brain Struct Funct. 2017 Mar;222(2):765-780. doi: 10.1007/s00429-016-1244-7. Epub 2016 Jun 16.
In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using (C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.
在一种新型动物模型八齿鼠中，我们检验了这样一个假设：除了遗传易感性外，早期生活应激（ELS）会导致注意力缺陷多动障碍样行为症状的病因及相关脑功能缺陷。由于先前的神经化学观察表明早期生活应激会损害多巴胺能功能，我们预测这些症状可用哌甲酯治疗使其恢复正常。与我们的假设一致，行为分析表明，反复的早期生活应激会导致运动活动亢进，并降低对情感相关听觉刺激的注意力。使用（C）-2-氟脱氧葡萄糖放射自显影术进行的功能成像显示，行为症状与前额叶、中脑边缘和皮质下脑区的代谢减退并行出现。最后，药物干预进一步证明行为和代谢功能障碍是由于多巴胺能神经传递受损所致。通过哌甲酯提高早期生活应激动物体内的多巴胺水平，可使运动活动亢进和注意力缺陷恢复正常，并以剂量依赖的方式改善脑代谢减退。
