Stress, exercise & depression: Neurochemical Mechanisms

描述：（由申请人提供）：暴露于生活压力是一种 抑郁和焦虑状态的诱发因素。既有行为 控制压力暴露和体力活动是有效的调节剂， 行为反应的压力，并可能通过类似的操作 神经化学机制不可控的，但不可控的，压力产生 长期行为抑郁症焦虑或习得性无助（LH） 致敏中缝背核（DRN）内的5-HT神经元。拟议 研究将检验行为控制和身体活动 两者都通过减弱应激诱导的蓝斑（LC）来预防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致敏。(1)我们将确定身体活动 防止LH的两种行为措施（穿梭箱逃逸和冻结）。（二） 我们将确定体力活动是否可以防止5-HT DRN的致敏作用 通过（a）测量5 HT神经元内的应激诱导的激活， DRN使用5 HT和c-Fos的双重免疫组织化学标记和（B） 使用体内测量DRN内应激诱导的5 HT释放 微透析(3)我们将确定身体活动和行为 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DRN中应激诱导的NE释放， (b)将逆行示踪剂（Flouro-Gold，FG）注入DRN， 定量特异性支配DRN的活性LC神经元的数量 使用FG和c-Fos的免疫组织化学标记，以及（c）驱动LC 在压力下逆转体力活动的保护作用， 应激源控制

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.