Mechanisms of Stress-Induced Changes in Behavior

描述(由Candiate提供)：创伤事件和慢性应激与创伤后应激障碍、抑郁和焦虑症等与应激相关的心理病理的发展有关。大多数应激相关障碍的动物模型使用严格控制的但人为的压力源，将这些发现扩展到更具生物相关性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攻击性的长期减少，以及随之而来的顺从和防御行为的增加。我们把这种应激诱导的激励性行为的改变称为条件性失败。目前的假设是，促肾上腺皮质激素释放激素(CRH)通过作用于中缝背核(DRN)中的5-羟色胺(5-HT)细胞和5-HT1a自身受体来调节条件性失败的获得和表达。具体目标1将检验这样一个假设，即DRN内的CRH神经传递调节条件性失败的获得和表达。《特殊目的2》将检验这一假说，即激活DRN内的5-HT1A自身受体调节条件性失败的获得和表达。此外，《特定目标2》将验证以下假设：社会挫败会激活5-羟色胺神经元，并使DRN中的5-HT1A自身受体变得不敏感。目前提案中的实验将提供关于压力相关疾病潜在的神经生物学机制的有价值的信息。

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.