Mechanisms of Stress-Induced Changes in Behavior

压力引起的行为变化的机制

• 批准号: 6887031
• 负责人: Matthew A Cooper
• 金额: $ 5.25万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2007-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6887031
• 关键词: behavioral /social science research tag; corticotropin releasing factor; dorsal raphe nucleus; ethology; hamsters; hormone inhibitor; hormone receptor; hormone regulation /control mechanism; neural plasticity; neuroendocrine system; neuropharmacologic agent; neurotransmitter agonist; postdoctoral investigator; psychological stressor; receptor sensitivity; serotonin receptor; social dominance

DESCRIPTION (provided by candidate): Traumatic events and chronic stress have been implicated in the development of stress-related psychopathologies such as post-traumatic stress disorder, depression, and anxiety disorders. Most animal models of stress-related disorders use tightly controlled, but artificial, stressors and it is critical to extend these findings to more biologically relevant stressors. In male Syrian hamsters, a single social defeat produces a prolonged reduction in territorial aggression and a concomitant rise in submissive and defensive behavior. We call this stress-induced change in agonistic behavior conditioned defeat. The overall hypothesis of the current proposal is that corticotrophin-releasing hormone (CRH) modulates the acquisition and expression of conditioned defeat by its actions on serotonin (5-HT) cells and 5-HT1a autoreceptors in the dorsal raphe nucleus (DRN). Specific Aim 1 will test the hypothesis that CRH neurotransmission within the DRN modulates the acquisition and expression of conditioned defeat. Specific Aim 2 will test the hypothesis that activation of 5-HT1a autoreceptors within the DRN modulates the acquisition and expression of conditioned defeat. Furthermore, Specific Aim 2 will test the hypotheses that social defeat activates 5-HT neurons and desensitizes 5-HT1a autoreceptors in the DRN. The experiments in the current proposal will provide valuable information on the neurobiological mechanisms underlying stress-related disorders.

描述（由候选人提供）：创伤事件和慢性压力与压力相关的心理病理学（例如创伤后应激障碍，抑郁症和焦虑症）的发展有关。大多数与压力相关疾病的动物模型都使用严格控制，但是人工压力源，至关重要的是将这些发现扩展到更具生物学相关的压力源。在男性叙利亚仓鼠中，一次社会失败会长期减少领土侵略，并随之而来的顺从和防御行为伴随着。我们称这种压力引起的激动行为的变化是有条件失败的。当前建议的总体假设是，促霉素释放激素（CRH）通过其对羟色胺（5-HT）细胞的作用和5-HT1A自身受体的作用来调节条件失败的采集和表达。具体目标1将检验以下假设：DRN中的CRH神经传递会调节条件失败的获取和表达。具体目标2将检验以下假设：DRN中5-HT1A自身受体的激活调节条件失败的获取和表达。此外，具体的目标2将检验社会失败激活5-HT神经元的假设，并使DRN中的5-HT1A自身受体脱敏。当前建议中的实验将提供有关与压力相关疾病的神经生物学机制的有价值信息。