Psychosozialer Streß und seine Auswirkungen auf das dopaminerge System

我们的建议旨在更好地了解慢性应激的病理生理学中中枢多巴胺系统的参与。在此之前，我们观察到树鼩的慢性社会心理应激诱导了中枢神经系统多巴胺受体的一系列复杂变化。这些改变包括大脑不同区域的受体上调（D2）和受体下调（D1和D2）。相比之下，多巴胺转运蛋白在任何脑区既不上调也不下调。我们推测，所观察到的多巴胺受体的局部变化发生在响应多巴胺释放的位点特异性改变。因此，我们建议寻求实验证据的发生在慢性心理社会压力的多巴胺释放的局部改变。体内脑微透析技术将用于监测细胞外多巴胺水平的变化。从这项研究中获得的数据将有望增加对慢性应激机制的识别。由于压力是神经精神疾病（如重性抑郁症）病因学中的一个主要诱发因素，我们的研究可能有助于对这种疾病的神经生物学基础的新见解。

Our proposal is aimed at obtaining a better understanding of the involvement of the central dopamine system in the pathophysiology of chronic stress. Previusly, we observed that chronic psychosocial stress in tree shrews induces a complex set of changes in dopamine receptors inthe central nervous system. The alterations include both receptor upregulation (D2) and receptor downregulation (D1 and D2) in different areas of the brain. In contrast, the dopamine transporter was neither upregulated nor downregulated in any brain region. We hypothesize that the observed local changes in dopamine receptors occur in response to sitespecific alterations in dopamine release. Therefore, we propose to seek experimental evidence for the occurrence of local alterations in the release of dopamine during chronic psychosocial stress. The in vivo cerebral microdialysis technique will be used to monitor changes in extracellular dopamine levels. Data arising from this research will be expected to add to the identification of the mechanism(s) underlying chronic stress. Because stress is a major predisposing factor in the etiology of neuropsychiatric illnesses such as major depression, our research may contribute to new insights in the neurobiological basis of this disorder.