Modulation of BNST 5-HT responses by corticosterone

皮质酮对 BNST 5-HT 反应的调节

• 批准号: 6887075
• 负责人: SAYAMWONG E. HAMMACK
• 金额: $ 4.73万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-11-16 至 2007-11-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6887075
• 关键词: anxiety; behavior test; behavioral /social science research tag; corticosterone; electrophysiology; fear; hormone regulation /control mechanism; laboratory rat; neurons; neurotransmitter transport; postdoctoral investigator; psychological stressor; serotonin receptor; startle reaction; stereotaxic techniques; thalamus; voltage /patch clamp

DESCRIPTION (provided by candidate): The bed nucleus of the stria terminalis (BNST) is believed to mediate anxiety-like states produced by exposure to uncontrollable, unpredictable, and/or chronic stress. These stressors are associated with long-term elevations in serotonergic (5-HT) and corticosterone release. Many individual BNST neurons exhibit both a 5-HT1A-mediated, anxiolytic, hyperpolarization and a 5-HT2-mediated, anxiogenic, depolarization in response to exogenous 5-HT application. The net response of each cell thus depends on the balance of these two responses. Chronic corticosterone has been shown to decrease 5-HT1A function and increase 5- HT2 function in several brain areas. This action within the BNST should shift the balance of 5-HT responses to favor more 5-HT2-mediated depolarizations, which, when combined with increased 5-HT release, could mediate anxiety. The specific aims in this proposal are designed to determine whether chronic corticosterone shifts the electrophysiological response of BNST neurons to favor 5-HT2-mediated function, and whether chronic corticosterone produces a more anxiogenic behavioral profile to BNST 5-HT.

描述（由候选人提供）：终纹床核（BNST）被认为是介导暴露于不可控制、不可预测和/或慢性应激所产生的焦虑样状态。 这些应激源与肾上腺素能（5-HT）和皮质酮释放的长期升高有关。 许多单个的BNST神经元表现出5-HT 1A介导的抗焦虑的超极化和5-HT 2介导的抗焦虑的去极化。 因此，每个细胞的净响应取决于这两种响应的平衡。 慢性皮质酮已被证明会降低5-HT 1A功能，并增加5-HT 2功能在几个大脑区域。 BNST内的这种作用应该改变5-HT反应的平衡，以有利于更多的5-HT 2介导的去极化，当与增加的5-HT释放相结合时，可以介导焦虑。 在这个建议的具体目标是旨在确定是否慢性皮质酮转移BNST神经元的电生理反应，有利于5-HT 2介导的功能，以及是否慢性皮质酮产生更多的焦虑行为的档案BNST 5-HT。