Psychosozialer Streß und seine Auswirkungen auf das dopaminerge System

我们的建议旨在更好地理解中枢多巴胺系统在慢性应激病理生理中的作用。以前，我们观察到树鼩的慢性社会心理压力会引起中枢神经系统多巴胺受体的一系列复杂变化。这种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，多巴胺转运体在任何大脑区域都没有上调或下调。我们假设观察到的多巴胺受体局部变化是对多巴胺释放位点特异性改变的反应。因此，我们建议寻求实验证据，以证明慢性社会心理应激过程中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。从这项研究中产生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（如重度抑郁症）病因学的主要诱发因素，我们的研究可能有助于对这种疾病的神经生物学基础有新的认识。

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.