Early Drug Exposure and Drug Reward Mechanisms

描述（由申请人提供）：根据PA-08-217，“药物滥用预防干预研究”，我们提出研究当前公认的注意缺陷多动障碍（ADHD）和药物成瘾行为表现共性的神经生物学机制。皮质多巴胺系统的改变可能在ADHD中发挥重要作用，兴奋剂疗法（如哌甲酯（MPH）、安非他明）的有益作用在于它们能够减少前额叶多巴胺功能的异常。在这种竞争性更新中，我们希望继续研究幼年大鼠兴奋剂治疗与后来的药物寻求行为之间的关系。在这里，我们将根据我们的发现：1)直接证实我们关于青少年皮质多巴胺功能异常的不良后果的初步观察；2)继续探索早期兴奋剂治疗效果的性别差异；3)进一步定义青少年时期兴奋剂暴露的多巴胺能后果，这可能是后来成瘾行为属性的基础。我们将使用行为学、神经化学和神经解剖学的方法来研究前额叶多巴胺功能和药物滥用相关问题的出现。最重要的是，我们将利用这些信息制定新的预防策略，可能用于减少这一高危人群的药物滥用。

DESCRIPTION (provided by applicant): Consistent with PA-08-217, "Drug Abuse Prevention Intervention Research", we propose to study neurobiological mechanisms that underlie currently recognized commonalities in behavioral manifestations of attention deficit hyperactivity disorder (ADHD) and drug addiction. Alterations in cortical dopamine systems may play a prominent role in ADHD, and that the beneficial effects of stimulant therapies (e.g. methylphenidate (MPH), amphetamines) lies in their ability to reduce abnormalities in prefrontal dopamine function. In this competitive renewal, we would like to continue our work on the relationship between stimulant therapy in juvenile rats and later drug-seeking behavior. Here, we will build upon our findings to: 1) directly confirm our preliminary observations regarding untoward later consequences of abnormalities in juvenile cortical dopamine function; 2) continue to explore gender-related differences in the effects of early stimulant treatment; and 3) further define dopaminergic consequences of stimulant exposure during the juvenile period that may underlie later behavioral attributes of addiction. We will use behavioral, neurochemical, and neuroanatomical approaches to investigate prefrontal dopamine function and the emergence of substance abuse-related problems. Most importantly, we will use this information to develop new, preventative strategies that may be used to reduce drug abuse in this high-risk population.