Brain DHA, Dopamine, and Behavior: Roles in ADHD

大脑 DHA、多巴胺和行为：在 ADHD 中的作用

• 批准号: 6868246
• 负责人: BETH LEVANT
• 金额: $ 18.79万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6868246
• 关键词: actigraphy; attention; attention deficit disorder; behavior; behavioral /social science research tag; biological models; developmental nutrition; dietary lipid; disease /disorder etiology; dopamine; dopamine receptor; dopamine transporter; dosage; gene environment interaction; juvenile animal; laboratory rat; malnutrition; methylphenidate; mother /embryo /fetus nutrition; neural plasticity; neurochemistry; neurogenesis; neuropharmacology; nutrition related tag; omega 3 fatty acid; pathologic process

DESCRIPTION (provided by applicant): A growing body of evidence suggests that inadequate incorporation of docosahexaenoic acid (DHA) in brain during development affects the CNS dopamine systems and, when combined with appropriate genetic and/or other epigenetic factors, contribute to the risk of developing ADHD or to the severity of the disease. This proposal addresses the HYPOTHESIS that low brain DHA levels during early development alter dopaminergic function producing hyperactivity and attentional deficits similar to the symptoms of ADHD. The OBJECTIVE of this study is to assess the behavioral and neurochemical effects of clinically-relevant variation in brain DHA content during early development. The Specific Aims will use a rat model to determine: 1. The effects of low brain DHA content during early development on activity and attentional processes in the developing rat. A force-plate actometer will be used to measure simultaneously assess activity and attentional processes in rats raised from conception on diets designed to modulate brain DHA content. 2. The effects of methylphenidate on hyperactivity and attentional processes in juvenile rats with low brain DHA content during early development. Dose-response effects of this drug used in the treatment of ADHD will be determined using the force-plate actometer. 3. The effects of low brain DHA content during early development on dopaminergic neurochemistry in juvenile rats. Dopamine content and turnover and the density of dopamine receptors and transporters will be assessed in specific brain regions. 4. The critical developmental period(s) when sufficient brain DHA content is essential for normal development of the dopamine systems. Treatment with DHA will be initiated at various time points between birth and weaning to determine when neuroplasticity is present. These experiments will show the relationship between brain DHA content and dopaminergic functioning and behavioral indices of hyperactivity and attentional processes. These findings will provide timely and important insights into mechanisms of brain development and perinatal nutrition and provide insights into the etiology of ADHD in humans. Such insights may identify a means by which certain risk factors for ADHD may be reduced or eliminated or the severity of the disease may be reduced through appropriate pre- and postnatal nutrition.

描述（由申请人提供）：越来越多的证据表明，发育过程中大脑中二十六六烯酸（DHA）的掺入不足会影响中枢神经系统多巴胺系统，并且在与适当的遗传和/或其他表观遗传因素结合使用时，会导致患ADHD的风险或疾病的严重性。该提议解决了以下假设：早期发育过程中的脑DHA水平较低，改变了多巴胺能功能产生多动症和注意力缺陷，类似于ADHD的症状。这项研究的目的是评估早期发育过程中脑部DHA含量与临床相关的临床差异变化的行为和神经化学作用。具体目的将使用大鼠模型确定： 1。早期发育过程中低脑DHA含量对发展大鼠活动和注意力过程的影响。力板表演计将用于测量从旨在调节脑DHA含量的饮食中提出的大鼠的活动和注意力过程的同时评估活动和注意力过程。 2。在早期发育过程中，甲基苯甲酸酯对脑DHA含量低的少年大鼠多动症和注意力过程的影响。该药物用于治疗多动症的药物的剂量反应效应将使用力板表演计确定。 3。早期发育过程中低脑DHA含量对少年大鼠多巴胺能神经化学的影响。多巴胺含量和周转率以及多巴胺受体和转运蛋白的密度将在特定的大脑区域进行评估。 4。当足够的大脑DHA含量对于多巴胺系统的正常发育至关重要时，关键的发育期。 DHA处理将在出生和断奶之间的各个时间点开始，以确定何时存在神经可塑性。 这些实验将显示脑DHA含量与多巴胺能功能和注意力过程的行为指数之间的关系。这些发现将及时，重要的见解对脑发育和围产期营养的机制，并提供对人类ADHD病因的见解。这种见解可能会确定一种方法可以减少或消除某些多动症的风险因素，或者通过适当的产后和后营养可以降低疾病的严重性。