Stress, exercise & depression: Neurochemical Mechanisms

描述：(申请人提供)：暴露于生活压力源是一种 抑郁和焦虑状态的易感因素。两者都是行为 对应激源暴露的控制和体力活动是对 对压力的行为反应，可能通过类似的 神经化学机制。无法控制，但不能控制的压力会产生 长期的行为抑郁！焦虑或习得性无助(LH) 敏化中缝背核(DRN)的5-羟色胺神经元。建议数 研究将检验行为控制和体力活动的假设 两者都通过减弱应激诱导的蓝斑(LC)来预防黄体生成素(LH) 去甲肾上腺素(NE)输出到DRN中的5-羟色胺(5-HT)神经元，从而 防止DRN的敏化。(1)我们将确定是否进行体力活动 防止两种行为措施的左侧(穿梭箱逃逸和冻结)。(2) 我们将确定体育活动是否能阻止5HTDRN的敏感化 通过(A)测量应激诱导的脑内5-羟色胺神经元的激活 5-羟色胺和c-Fos双重免疫组织化学标记DRN及(B) 在体测应激诱导的DRN内5-羟色胺释放 微透析。(3)我们将确定是否同时进行身体活动和行为 控制通过减少来自LC的NE输入来防止DRN的敏化 (A)使用体内微透析测量应激诱导的DRN中NE的释放， (B)将逆行示踪剂(氟金，FG)注入DRN，并 对特异性支配DRN的活跃LC神经元数量进行量化 使用免疫组织化学标记FG和c-Fos，以及，(C)驱动LC 在应激期间逆转体力活动的保护作用 压力源控制。

DESCRIPTION: (provided by applicant): Exposure to life stressors is a predisposing factor for states of depression and anxiety. Both behavioral control over stressor exposure and physical activity are potent modulators of the behavioral response to stress, and may operate through similar neurochemical mechanisms. Uncontrollable, but not controllable, stress produces long-term behavioral depression! anxiety or learned helplessness (LH) by sensitizing 5HT neurons in the dorsal raphe nucleus (DRN). The proposed research will test the hypothesis that behavioral control and physical activity both prevent LH by attenuating stress-induced locus coeruleus (LC) norepinephrine (NE) output to serotonin (5HT) neurons in the DRN, thereby preventing sensitization of the DRN. (1) We will determine if physical activity prevents two behavioral measures of LH (shuttle box escape and freezing). (2) We will determine if physical activity prevents sensitization of 5HT DRN neurons by (a) measuring stress-induced activation of 5HT neurons within the DRN using double immunohistochemical labeling for 5HT and c-Fos and (b) measuring stress-induced 5HT release within the DRN using in vivo microdialysis. (3) We will determine if both physical activity and behavioral control prevent sensitization of the DRN by reducing NE input from .the LC by (a) measuring stress-induced NE release in the DRN using in vivo microdialysis, (b) injecting a retrograde tracer (Flouro-Gold, FG) into the DRN and quantifying the number of active LC neurons that specifically innervate the DRN using immunohistochemical labeling for FG and c-Fos and, (c) driving the LC during stress to reverse the protective effect of physical activity and stressor control.