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时产生的行为和生理改变中起作用。支持这一结论的数据来自以下发现：(a)急性应激可以诱导中枢和周围的促炎细胞因子产生，(b)促炎细胞因子的管理产生许多与急性应激暴露相同的行为和生理后果，以及(c)抑制促炎细胞因子活性抑制或减轻急性应激暴露的一些行为和生理后果。这些数据表明，应激反应中细胞因子的产生可能为应激相关疾病的病因提供新的见解。也许最广泛使用的动物压力模型之一是强迫游泳测试。在这个压力源中，老鼠被迫在一个无法逃脱的圆柱形水里游泳。经过一段以反复尝试逃跑为特征的初始行为激活期后，老鼠会采取一种典型的一动不动的姿势，这种姿势被概念化为行为绝望。考虑到最近细胞因子介导一些压力相关行为的观点，我们探讨了促炎细胞因子白介素01 （IL-1）是否会在被迫游泳的大鼠中升高。我们的初步结果表明，在强制游泳后，所有外周组织（血液、垂体和脾脏）的IL-1都有明显的增加。这些数据提出了在强迫游泳应激源中观察到的不动反应可能由IL-1介导的可能性。因此，本提案的目的是表征游泳应激诱导IL-1增加的时间过程，并确定IL-1的增加是否与强迫游泳暴露期间观察到的行为变化在功能上相关。

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.