NEURAL MECHANISMS UNDERLYING ADAPTIVE COPING SOCIALLY INDUCED ANXIETY

适应性应对社会引起的焦虑的神经机制

• 批准号: 7627578
• 负责人: Gina L Forster
• 金额: $ 15.49万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627578
• 关键词: Adaptive Behaviors; Amygdaloid structure; Anxiety; Anxiety Disorders; Behavior; Behavioral; Centers of Research Excellence; Complex; Computer Retrieval of Information on Scientific Projects Database; Corticotropin-Releasing Hormone; Development; Disinhibition; Disruption; Equilibrium; Event; Freezing; Funding; Grant; Human; Infusion procedures; Institution; Link; Medial; Modeling; Neurohormones; Neurotransmitters; Outcome; Output; Play; Prefrontal Cortex; Production; Rattus; Research; Research Personnel; Resources; Role; Serotonin; Site; Source; Stress; Stressful Event; System; Testing; United States National Institutes of Health; biological adaptation to stress; coping; dorsal raphe nucleus; neural circuit; neuromechanism; neuronal cell body; raphe nuclei; response; social

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Expression of adaptive stress-related behavior, and also of maladaptive stress and anxiety states, is strongly linked with the neurotransmitter serotonin (5HT) and the neurohormone corticotropin-releasing factor (CRF; Dunn and Berridge, 1990; Millan, 2003). Converging evidence suggests that 5HT cell body groups in the raphe nuclei play differential roles in the production of adaptive stress responses (Deakin, 1998; Lowry, 2002; Forster et al., 2004b). Infusions of CRF into the dorsal raphe nucleus (dRN) induces freezing behavior in rats (Forster et al., 2004b) ? an ecologically adaptive behavior expressed during, or in anticipation of, an aversive event (Fendt and Fanselow, 1999). Freezing behavior induced by CRF actions in the dRN may be a result of increased 5HT activity in the amygdala, since 5HT levels in the amygdala increases immediately during stress, and 5HT activity in this region is required for induction of freezing behavior (Macedo et al., 2002). In contrast, increased 5HT release in the medial prefrontal cortex (mPFC) is associated with cessation of CRF-elicited freezing behavior (Forster et al., 2004b). These increased mPFC 5HT levels following freezing behavior are actually derived from the median raphe (mRN), and may serve to limit stress responses adaptively (i.e. coping) (Forster et al., 2004b). These findings suggest a complex interplay is required between raphe nuclei and their terminal sites for production of adaptive behavioral responses and coping during stressful events. We hypothesize that during, or in anticipation of, an aversive event, CRF released into the dRN causes increased 5HT output to the amygdala, which facilitates expression of stress-related behavior, and also results in disinhibition of the mRN to allow increased mPFC 5HT activity to facilitate coping. Furthermore, we suggest that long-term alterations to this neural circuitry contribute to anxiety disorders by increasing stress responsiveness and reducing coping ability during the anticipation of aversive outcomes. Here we hypothesize that increased stress and anxiety behaviors as a result of social defeat in rats (a model of human socially induced anxiety) are a function of disruption to the balance between raphe 5HT systems and amygdala/mPFC 5HT activity, as regulated by CRF. Testing these hypotheses is central to the current COBRE themes, advancing our understanding of the neural circuitry underlying adaptive stress behavior and the development of maladaptive anxiety states.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 适应性应激相关行为以及适应不良的压力和焦虑状态的表达与神经递质5-羟色胺（5HT）和神经激素皮质激素释放因子（CRF; Dunn and Berridge，1990; Millan，2003年）密切相关。 融合的证据表明，Raphe核中的5HT细胞体组在适应性应激反应的产生中起差异作用（Deakin，1998; Lowry，2002; Forster等，2004b）。 将CRF输注到背侧Raphe核（DRN）中会诱导大鼠的冻结行为（Forster等，2004b）？在厌恶事件中或期望发生的生态适应性行为（Fendt and Fanselow，1999）。 DRN中CRF作用引起的冻结行为可能是杏仁核中5HT活性增加的结果，因为杏仁核的5HT水平在压力期间立即增加，并且该区域的5HT活性是诱导冰冻行为所必需的（Macedo等人，Macedo等，2002）。 相比之下，内侧前额叶皮层（MPFC）中的5HT释放增加与停止CRF引用的冻结行为有关（Forster等，2004b）。 这些增加的冰冻行为后MPFC 5HT水平实际上是从中间Raphe（MRN）得出的，并且可以自适应地限制压力反应（即应对）（Forster等，2004b）。 这些发现表明，在压力事件期间，Raphe Nuclei及其终端位点之间需要复杂的相互作用，以生产适应性行为反应和应对。 我们假设在厌恶事件中或预期的是，释放到DRN中的CRF会增加对杏仁核的5HT输出，从而促进与应力相关行为的表达，也导致MRN抑制以增加MPFC 5HT活性以促进应对。 此外，我们建议对这种神经回路的长期改变通过增加压力反应能力并降低厌恶结局的应对能力来导致焦虑症。 在这里，我们假设由于大鼠的社交失败（人类社会诱发的焦虑模型）而增加的压力和焦虑行为是对Raphe 5HT系统与杏仁核/MPFC 5HT活动之间平衡的破坏的函数，该活动受CRF的调节。 测试这些假设对于当前的毛病主题至关重要，它促进了我们对适应性压力行为的神经回路的理解和适应不良焦虑状态的发展。