Behavioral Despair and Interleukin-1

近年来，越来越多的人认识到，促炎细胞因子在暴露于心理应激源所产生的行为和生理变化中发挥了作用。支持这一结论的数据来自以下发现：(A)急性应激可诱导中枢和外周的促炎细胞因子的产生，(B)促炎细胞因子的应用产生许多与急性应激暴露相同的行为和生理后果，以及(C)阻断促炎细胞因子活动抑制或减轻急性应激暴露的某些行为和生理后果。这些数据表明，应激时细胞因子的产生可能为应激相关疾病的病因学提供新的见解。也许最广泛使用的应激动物模型之一是强迫游泳测试。在这种压力下，老鼠被迫在一个无法逃脱的水缸中游泳。在经历了以反复尝试逃跑为特征的行为激活的最初阶段后，大鼠采取了一种特征的静止姿势，这种姿势被概念化为行为绝望。鉴于最近有观点认为细胞因子介导了一些应激相关行为，我们探索了促炎细胞因子IL-1在被迫游泳的大鼠中是否会升高。我们的初步结果显示，在强迫游泳后，所有被检查的外周组织(血液、垂体和脾)中的IL-1都有强劲的增加。这些数据增加了在强迫游泳应激时观察到的不动反应可能是由IL-1介导的可能性。因此，本研究的目的是描述游泳应激诱导的IL-1增加的时间过程，并确定IL-1的增加是否在功能上与强迫游泳暴露期间观察到的行为变化有关。

In recent years, there has been increasing recognition that pro- inflammatory cytokines play a role in the behavioral and physiological alterations produced by exposure to psychological stressors. The data to support this conclusion comes from the findings that (a) acute stress can induce pro-inflammatory cytokine production both centrally and peripherally, (b) administration of pro-inflammatory cytokines produces many of the same behavioral and physiological consequences as acute stress exposure, and (c) blockade of pro-inflammatory cytokine activity inhibits or attenuates some behavioral and physiological consequences of acute stressor exposure. These data have led to the suggestion that production of cytokines in response to stress may provide novel insight into the etiology of stress-related disorders. Perhaps one of the most widely used animal models of stress is the forced swim test. During this stressor, rats are forced to swim in a cylinder of water from which there is no escape. After an initial period of behavioral activation characterized by repeated attempts to escape, rats then adopt a characteristic posture of immobility that has been conceptualized as behavioral despair. Given recent notions that cytokines mediate some stress-related behaviors, we explored whether the pro-inflammatory cytokine Interleukin01 (IL-1) would be elevated in rats that have been forced to swim. Our preliminary results demonstrate a robust increase in IL-1 in all peripheral tissues examined (blood, pituitary, and spleen) immediately after the forced swim session. These data raise the possibility that the immobility response observed during the forced swim stressor may be mediated by IL-1. Thus, the goal of this proposal is to characterize the time-course of the swim stress induced increase in IL-1 and determine whether the increase in IL-1 is functionally related to the changes in behavior observed during forced swim exposure.