Psychosozialer Streß und seine Auswirkungen auf das dopaminerge System

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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.