Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.
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 (14C)-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.
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.
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J
Bock
Institute of Biology, Department of Zoology/Developmental Neurobiology, Otto von Guericke University, Leipziger Str. 44, 39118, Magdeburg, Germany.
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S
Breuer
Institute for Biology, Human Biology, University of Leipzig, 04103, Leipzig, Germany.
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G
Poeggel
Institute of Biology, Department of Zoology/Developmental Neurobiology, Otto von Guericke University, Leipziger Str. 44, 39118, Magdeburg, Germany. katharina.braun@ovgu.de.|Center for Behavioral Brain Science, Otto von Guericke University Magdeburg, Magdeburg, Germany. katharina.braun@ovgu.de.
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Braun
D000818:Animals; D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D007175:Impulsive Behavior / Q000187:drug effects; D008774:Methylphenidate / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects; D046329:Octodon; D051381:Rats; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000523:psychology*
D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate
Childhood adversity; Dopamine; Limbic; Prefrontal cortex; Stress