Topography of Serotonin Dysfunction

描述(申请人提供)：目前尚不清楚5-羟色胺如何在抑郁症、药物成瘾和其他疾病中的大脑功能障碍中循环。了解5-羟色胺神经传递在精神病理学中的作用，是因为5-羟色胺系统最显著的特征之一：它的神经解剖学。在这个项目中，我们研究了抑郁症和尼古丁戒断的动物模型中5-羟色胺神经元功能的变化，以及抗抑郁药物治疗后的变化。我们的工作试图调和行为药理学和神经解剖学，以解决该领域的一些相互矛盾的发现。压倒一切的假设是，抑郁时5-羟色胺神经元的激活存在局部组织的变化，这些变化可以通过抗抑郁药物治疗来解决。此外，我们还研究了5-HT1a受体介导的反馈抑制如何与改变的5-羟色胺神经元活性模式相协调地改变。最后，我们考察了激活状态的局部选择性变化对行为的功能影响。具体目的是结合细胞、系统和行为方法来了解5-羟色胺神经传递的功能和功能障碍。这项研究计划的长期目标是更好地了解5-羟色胺在情感性和成瘾障碍中的作用。

DESCRIPTION (provided by applicant): It remains poorly understood how serotonin circuits in the brain dysfunction in depression, drug addiction and other disorders. Understanding the role of serotonin neurotransmission in psychopathology is complicated by one of the most salient features of the serotonin system: its neuroanatomy. In this project we examine how serotonin neuron function changes in animal models of depression and nicotine abstinence, and after antidepressant treatment. Our work seeks to reconcile behavioral pharmacology with neuroanatomy to resolve some of the contradictory findings in the field. The over-riding hypothesis is that there are topographically organized changes in the activation of serotonin neurons in depression and these are resolved by antidepressant treatment. In addition, we examine how feedback inhibition mediated by 5-HT1A receptors changes in coordination with altered patterns of serotonin-neuron activity. Finally we examine the functional impact of topographically selective changes in activation state on behavior. The specific aims integrate cellular, systems and behavioral approaches to understand function and dysfunction of serotonin neurotransmission. The broad long-term goal of this research program is to provide a better understanding of the role of serotonin in affective and addictive disorders.