Depression and heart failure associated cardiovascular pathology

抑郁症和心力衰竭相关的心血管病理学

• 批准号: 6704840
• 负责人: ALAN Kim JOHNSON
• 金额: $ 17.79万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-21 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6704840
• 关键词: behavioral /social science research tag; cardiovascular disorder risk; depression; disease /disorder model; heart failure; heart function; laboratory rat; model design /development; pleasure; psychosomatic disorders; reinforcer; serotonin; stress

Depression is both a debilitating psychological disorder and a condition that affects an individual's physical well-being. Depression is a recognized risk factor for heart disease. Research has demonstrated that depression predisposes an individual to myocardial infarction, sudden death, atherosclerosis, thrombosis and arrhythmias. While the behavioral and cognitive aspects of depression have been studied extensively, there has been much less research investigating the mechanisms responsible for the physiological consequences of mood disorders. Exposure of rodents to a series of chronic mild stressors (CMS) generates key behavioral characteristics of human depression that are observable and quantifiable. The CMS model of experimentally-induced depression (ID) mimics the reduced responsiveness to pleasurable stimuli (anhedonia)which is a pivotal diagnostic criterion seen in depression. In the CMSdD model, anhedonia is induced by presenting mild unpredictable stressors (e.g., paired housing, stroboscopic illumination, white noise) of varying durations. In rats,anhedonia is operationally defined as a decrease in responding for a previously demonstrated reinforcer (reward). Recently, we have begun to characterize cardiovascular function in rats with CMS-ID. We have found that rats exposed to CMS for 4 weeks showed anhedonia along with cardiovascular alterations. Similar to patients with depression and with heart failure,CMSgD rats had elevated resting heart rates and reduced heart rate variability. In addition, rats exposed to CMS have increased susceptibility to experimentally-induced premature ventricular contractions. In other studies investigating the behavioral consequences of heart failure, we have found evidence of anhedonia (i.e., experimental depression) in rats with experimental myocardial infarction. The proposed research program will extend our characterization of the cardiovascular changes that accompany experimentally-induced depression and investigate the role of brain serotonergic mechanisms that are hypothesized to be common in the mediation of cardiovascular alterations that accompany both experimental depression and experimental heart failure.

抑郁症既是一种使人衰弱的心理障碍，也是一种影响个人身体健康的疾病。 抑郁症是公认的心脏病危险因素。研究表明，抑郁症使人容易发生心肌梗塞、猝死、动脉粥样硬化、血栓形成和心律失常。虽然抑郁症的行为和认知方面已经得到了广泛的研究，但调查情绪障碍生理后果的机制的研究要少得多。 啮齿类动物暴露于一系列慢性轻度应激源（CMS）产生了人类抑郁症的关键行为特征，这些特征是可观察和可量化的。实验诱导抑郁症（ID）的CMS模型模拟了对愉快刺激的反应性降低（快感缺失），这是抑郁症中的关键诊断标准。 在CMSdD模型中，快感缺失是通过呈现轻度不可预测的应激源（例如，成对外壳、频闪照明、白色噪声）。在大鼠中，快感缺失在操作上被定义为对先前证明的奖赏（奖励）的反应减少。最近，我们已经开始表征CMS-ID大鼠的心血管功能。我们发现，暴露于CMS 4周的大鼠表现出快感缺失沿着 心血管改变与抑郁症和心力衰竭患者相似，CMSgD大鼠的静息心率升高，心率变异性降低。此外，暴露于CMS的大鼠对实验诱导的室性早搏的易感性增加。在其他调查心力衰竭行为后果的研究中，我们发现了快感缺乏的证据（即，实验性抑郁症）与实验性心肌梗死大鼠。 拟议的研究计划将扩展我们对实验性抑郁症伴随的心血管变化的表征，并研究假设在伴随实验性抑郁症和实验性心力衰竭的心血管改变的介导中常见的脑神经递质机制的作用。