抑郁症已成为最主要的精神疾患，应激在抑郁症的发生发展中具有重要作用。抑郁症患者血锌降低，高锌摄入可产生抗抑郁效应，且抗抑郁治疗后可提高血锌水平。我们前期发现应激可致血锌和海马锌显著下降，并导致大鼠出现抑郁样行为学变化，提示锌在应激致抑郁发生发展中具有重要作用，应激致海马锌下降可能是应激致抑郁样行为学变化的物质基础。本研究拟建立应激致抑郁大鼠模型和细胞应激模型，通过锌代谢实验、神经生物学检测、行为学检测、分子生物学和免疫学技术等观察应激致抑郁大鼠锌代谢变化及其机制；低锌导致动物抑郁样行为改变的机制；高锌补充后能否改善动物抑郁样行为学变化及其机制；抗抑郁治疗后，锌水平变化的规律及其机制；补锌和抗抑郁治疗是否具有协同效应？锌受体GPR39在应激致抑郁过程中的作用及机制研究。研究结果不仅有助于应激致抑郁样行为学变化的可能原因及其机制，而且在此基础上为研究抑郁症病因、发病机制及治疗措施的研究提供理论

Depression is a major psychiatric disease that is associated with high rates of suicide and is considered to be one of the most important caused of human disability. The mechanisms of the psychopathology of depression are multifaceted. Therefore, the search for new antidepressant therapies is an area of considerable interest. Stress circumstance plays a role in the development of depression. Recent clinical observations demonstrated a reduced serum zinc concentration in the depressed patients. And more interesting, the low serum zinc was normalized after successful antidepressant therapy. Our previous studies revealed that stress could induce decreased zinc levels in serum and hippocampus and depression-like behavior in rats. These discoveries suggested that zinc may play a role in the development of depression. The decreased zinc in hippocampus may be the cause of the depression-like behavior in stress-induced rats. In present studies, the effects of zinc in stress-induced depression were examined by zinc metabolism, behavior, molecular biology, immunology and neurobiology tests after establishing stress-induced depression rat model. The aims of present studies were to explain the zinc metabolism in stress-induced depression rats and its possible mechanisms; the effects of low zinc intake on behavior in rats and its possible mechanism; the effects of high zinc intake on behavior in rats and its possible mechanism; the effects of antidepressant therapy on zinc metabolism and its possible mechanism; the effects of combination of zinc and antidepressant on behavior in stress-induced rats and the effects of zinc receptor GPR39 on stress-induced depression and its mechanisms. The present study will be helpful to not only understanding the possible mechanisms of stress-induced depression, but also providing possible solutions to stress-induced depression.