Facilitating Extinction in Adolescents

促进青少年的灭绝

基本信息

批准号：
7690766
负责人：
Heather C Brenhouse
金额：
$ 11.32万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-30 至 2010-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): As we endeavor to understand the mechanisms and treatment avenues for drug seeking, it is crucial to address unique populations. The developing brain responds differently to drugs of abuse such as stimulants, with a particular window of vulnerability for addiction in adolescence. Extinction of drug-seeking behavior is an integral part of drug addiction treatment, and recently we reported that adolescents are more resistant to extinction relative to adults. Importantly, adolescence also represents a critical period of development when intervention could prevent a lifetime of recurring drug addiction. Recently, research has converged on the ideas that, 1) adolescents are a vulnerable population for drug addiction and display delayed extinction of drug seeking behaviors, 2) extinction and relapse of drug-seeking are mediated through motivational conditioning circuitries, 3) the dopaminergic receptor microcircuitry within the prefrontal cortex (PFC) mediates motivational conditioning, and 4) the adolescent dopamine receptor profile within the PFC is unique. The proposed experiments will build on our recent observation that the D1 dopamine receptor is transiently overproduced on PFC outputs to the nucleus accumbens during adolescence. This application applies these findings to a working hypothesis that may lead to novel treatment strategies targeted to adolescents. These studies serve as a foundation for a crucial line of research into the treatment of adolescent drug addiction, focusing on the extinction of drug-seeking behavior. PUBLIC HEALTH RELEVANCE: Adolescence represents a unique stage of cortical development which results in a particular vulnerability to drug addiction. Heightened responsiveness to drug- associated cues, and diminished ability to respond to less-potent stimuli, render adolescents resistant to extinction of drug-seeking. Therefore, treatment of drug addiction during this critical period of brain development will require distinct strategies from those used for adults, such as cortically-targeted pharmacologic intervention.

描述（由申请人提供）：当我们努力了解寻求药物的机制和治疗途径时，解决独特的人群至关重要。发育中的大脑对滥用药物（例如兴奋剂）的反应不同，在青春期中特定的成瘾脆弱性。寻求药物行为的灭绝是药物成瘾治疗中不可或缺的一部分，最近我们报道，相对于成年人，青少年对灭绝更具抵抗力。重要的是，当干预措施可以防止重复的药物成瘾寿命时，青春期也代表了一个关键的发展时期。最近，研究已经融合了以下思想：1）青少年是吸毒行为的脆弱人群，表现出延迟的灭绝，2）2）灭绝和寻求药物的复发是通过动机调节循环系统来介导的，3）多巴胺能在乳状细胞（PFC）中的多巴胺能微纤维纤维（PFC）的动机（PFC）中的动机， PFC中的受体轮廓是唯一的。提出的实验将基于我们最近的观察结果，即D1多巴胺受体在青春期对伏隔核的PFC输出瞬时产生。该应用程序将这些发现应用于有效的假设，该假设可能导致针对青少年的新型治疗策略。这些研究是对青少年药物成瘾治疗的关键研究的基础，重点是寻求药物行为。公共卫生相关性：青春期代表了皮质发育的独特阶段，导致特殊的药物成瘾脆弱性。对药物相关线索的反应性提高，并降低了对较低功能刺激的反应能力，使青少年抵抗了灭绝药物寻求药物的能力。因此，在这个关键的大脑发育期间，药物成瘾的治疗将需要与成年人使用的策略（例如皮质靶向的药理学干预措施）的不同策略。