Mechanisms of Stress-Induced Changes in Behavior

描述（由候选人提供）：创伤事件和慢性压力与压力相关的精神病理学的发展有关，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，但人为的，压力源，这是至关重要的，以扩大这些研究结果，以更生物相关的压力源。在雄性叙利亚仓鼠中，单一的社会失败会导致领土侵略的长期减少，并伴随着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的变化称为条件性失败。目前的建议的总体假设是，促肾上腺皮质激素释放激素（CRH）调节收购和条件性失败的表达，其行动对5-羟色胺（5-HT）细胞和5-HT 1a的中缝背核（DRN）的自身受体。具体目标1将测试的假设，CRH神经传递DRN调制收购和条件失败的表达。具体目标2将测试DRN内5-HT 1a自身受体的激活调节条件性失败的获得和表达的假设。此外，具体目标2将测试社交失败激活DRN中的5-HT神经元并使5-HT 1a自身受体脱敏的假设。本研究的实验将为研究应激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.