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: 7091446
• 负责人: BETH LEVANT
• 金额: $ 19.38万
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7091446
• 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，发育期间大脑中二十二碳六烯酸（DHA）的掺入不足会影响中枢神经系统多巴胺系统，并且当与适当的遗传和/或其他表观遗传因素结合时，会增加发生ADHD的风险或疾病的严重性。这一建议提出了一个假说，即在早期发育过程中大脑DHA水平低会改变多巴胺能功能，产生类似多动症症状的多动和注意力缺陷。本研究的目的是评估早期发育期间脑DHA含量的临床相关变化对行为和神经化学的影响。具体目标将使用大鼠模型来确定：