Neuroendocrine Effects of Repeated Social Defeat

反复社交失败对神经内分泌的影响

• 批准号: 0115212
• 负责人: Seema Bhatnagar
• 金额: $ 14.62万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0115212&HistoricalAwards=false
• 关键词: Neuroendocrine; Effects; Repeated; Social; Defeat

Chronic or repeated exposure to stress produces plasticity in a number of neural systems, including those that regulate the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis has widespread effects on physiology and behavior, including modulation of metabolism and cardiovascular function. Changes in basal activity as well as subsequent stress-induced HPA activity are seen in animals exposed to repeated stress such as cold or restraint. This project uses a more naturalistic model of stress in rodents, that of repeated exposure to social defeat. Defeat in the context of social environment, including which individual is a resident or an intruder in the local area, is a familiar situation in the natural life of many social rodents such as rats. Although a single defeat produces neuroendocrine and behavioral effects that last a few weeks, it is more common in the wild to have an individual animal regularly subjected to defeat. Therefore, repeated defeat in rats represents a potentially powerful model for the study of neural plasticity associated with chronic, repeated stress. Using a novel combination of molecular biology and behavior, the goals of this project are to 1) characterize how basal and stress-induced HPA activity change in rats subject to repeated defeat; 2) study the specific role of the paraventricular thalamus, a brain region that inhibits HPA responses in other stress situations, in the repeated defeat paradigm; and 3) identify novel brain regions in which activity is increased by repeated defeat, since these are potential sites of regulation of HPA activity. Results will be important for identifying novel brain circuitry involved in the modulation of behavior, and with an impact on our understanding more about the role of social versus physical stress, and about the evolution of sociality. This project also fosters the career of a new investigator who combines an unusual background in molecular biology and behavior.

长期或反复暴露于压力会在许多神经系统中产生可塑性，包括调节下丘脑-垂体-肾上腺（HPA）轴的神经系统。 HPA轴对生理和行为具有广泛的影响，包括调节代谢和心血管功能。 基础活动的变化以及随后的应激诱导的HPA活性在暴露于反复应激（如寒冷或束缚）的动物中可见。 这个项目使用了一个更自然的啮齿动物压力模型，即反复暴露于社会失败。 在社会环境的背景下失败，包括哪个个体是当地的居民或入侵者，是许多社会啮齿动物（如大鼠）自然生活中熟悉的情况。 虽然一次失败会产生持续几周的神经内分泌和行为影响，但在野外，个体动物经常遭受失败的情况更为常见。 因此，大鼠的反复失败代表了一个潜在的强大模型，用于研究与慢性重复应激相关的神经可塑性。 本研究采用分子生物学和行为学相结合的新方法，目的是：1）研究反复失败大鼠基础和应激诱导的HPA活性变化; 2）研究室旁丘脑在反复失败范式中的特殊作用，室旁丘脑是一个在其他应激情况下抑制HPA反应的脑区;和3）鉴定新的脑区域，其中活性通过反复失败而增加，因为这些是HPA活性调节的潜在位点。 研究结果对于识别参与行为调节的新大脑回路非常重要，并对我们更多地了解社会压力与身体压力的作用以及社会性的进化产生影响。 该项目还培养了一个新的研究者的职业生涯，他结合了分子生物学和行为学的不寻常背景。