Mechanisms of Stress-Induced Changes in Behavior

描述（由候选人提供）：创伤性事件和慢性压力与压力相关的精神病理的发展有关，如创伤后应激障碍、抑郁症和焦虑症。大多数压力相关疾病的动物模型使用严格控制的人工压力源，将这些发现扩展到更多生物学相关的压力源是至关重要的。在雄性叙利亚仓鼠中，一次社会失败会导致领土侵略的长期减少，并伴随而来的顺从和防御行为的增加。我们把这种由压力引起的对抗行为变化称为条件失败。目前提出的总体假设是，促肾上腺皮质激素释放激素（CRH）通过作用于中脑背核（DRN）的5-羟色胺（5-HT）细胞和5-HT1a自身受体来调节条件挫败的获得和表达。特异性目标1将测试DRN内CRH神经传递调节条件失败的获得和表达的假设。特异性目标2将验证DRN内5-HT1a自受体的激活调节条件失败的获得和表达的假设。此外，Specific Aim 2将测试社交失败激活5-HT神经元并使DRN中的5-HT1a自受体脱敏的假设。当前提案中的实验将为压力相关疾病的神经生物学机制提供有价值的信息。

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.