Gene Expression Profiling of Drug Addiction Models

描述(由申请人提供)： 许多行为病理都源于服从于奖赏的神经系统的失调。例如，对奖励刺激的反应受损出现在戒毒和抑郁中，而过度追求自我毁灭的奖励发生在药物滥用和躁狂中。在这项提议中，我们通过将微阵列技术应用于大脑奖励回路中的站点，研究了三种相互关联的药物成瘾和情绪障碍的大鼠模型。第一和第二个目标是分别发现苯丙胺和尼古丁戒断后奖赏敏感度降低的基因表达相关性。在第三个目标中，我们确定了甲基苯丙胺从稳定给药到升级给药的基因表达谱。希望这项研究将有助于深入了解情绪和药物滥用障碍的分子基础，并为这些疾病的治疗方法的发展提供新的靶点。

DESCRIPTION (provided by applicant): Much behavioral pathology stems from dysregulation of the neural systems subserving reward. For example, impaired responsiveness to rewarding stimuli occurs in drug withdrawal and depression while there is excessive pursuit of self-destructive rewards in drug abuse and mania. In this proposal, we study three interrelated rat models of drug addiction and mood disorder by applying microarray technology to sites within the brain's reward circuits. The first and second aim are to discover gene expression correlates of the episode of diminished reward sensitivity that follows amphetamine and nicotine withdrawal, respectively. In the third aim, we determine the gene expression profile of the transition from stable to escalating self-administration of methamphetamine. It is hoped that this research will foster insight into the molecular basis of mood and substance abuse disorders as well as providing novel targets for the development of treatments for these conditions.