Neural Substrates /Appetitive Behavior /Mood /Motivation

神经基质/食欲行为/情绪/动机

• 批准号: 6803146
• 负责人: ERIC J. NESTLER
• 金额: $ 187.48万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6803146
• 关键词: antidepressants; appetite regulatory center; behavior test; behavioral /social science research tag; behavioral genetics; clinical research; depression; emotions; gene targeting; genetically modified animals; hypothalamus; laboratory mouse; laboratory rat; motivation; nucleus accumbens; psychopharmacology; stress

DESCRIPTION (provided by applicant): The objective of this new Conte Center is to study the role of the brain's appetitive neural circuits in the regulation of mood and motivation as they relate to depression and antidepressant action. The program of research contains three major strengths. First, is the multidisciplinary nature of our ongoing and proposed research. Each research area represents an integration of molecular, cellular, pharmacological, and behavioral levels of analysis aimed at obtaining a more complete understanding of the neurobiology of mood. Second, is the integration of our basic science research with the investigation of clinical populations. Third, is the extraordinary degree of integration of the various Projects to examine highly related aspects of the central hypothesis of the Center. While research in depression has focused largely on hippocampus and cerebral cortex, other neural circuits possibly involved have received much less attention. This Center focuses on one of these other circuits, namely, appetitive regions of brain, including nucleus accumbens and hypothalamus, important for motivation, reward, appetite, sleep, psychomotor activity, and circadian rhythms. A focus on these appetitive circuits makes sense given the degree to which abnormalities in these various domains are seen in patients with depression and other mood disorders. Indeed, we have obtained substantial evidence, presented in this application, for the importance of these appetitive circuits in animal models of depression. The Center is organized into a small Coordination Core, two scientific Cores, and five Projects. The Transgenic Core is responsible for providing state-of-the-art molecular tools to Center investigators, while the Behavioral Core is responsible for providing to individual Projects an extremely broad battery of behavioral tests in mice and rats relevant to mood and motivation. Project 1 is focused on the transcription factor CREB as a key regulator of appetitive circuits and its role in mood and motivation. Subsequent Projects evaluate a series of other molecular signals in these neural pathways that are both important regulators of CREB function and important effectors in mediating CREB's behavioral phenotype. Project 2 focuses on BDNF; Project 3 focuses on three hypothalamic peptides, MSH, orexin (hypocretin), and MCH; Project 4 focuses on NPAS2 and other circadian genes; Project 5 focuses on RGS proteins, in particular, RGS9 and RGS16.

描述（由申请人提供）：这个新的孔戴中心的目的是研究大脑的食欲神经回路在与抑郁症和抗抑郁药相关的情绪和动机调节中的作用。研究计划包含三个主要优势。首先，我们正在进行的和拟议的研究的多学科性质。每个研究领域代表分子，细胞，药理和行为分析水平的整合，旨在获得对情绪神经生物学的更完整理解。其次，我们的基础科学研究与临床人群的研究相结合。第三，是各种项目的非凡程度，以检查中心中心假设的高度相关方面。 尽管抑郁症的研究主要集中在海马和大脑皮层上，但其他可能涉及的神经回路受到了较少的关注。该中心重点关注其他电路之一，即大脑的开胃菜区域，包括伏隔核和下丘脑，对动机，奖励，食欲，睡眠，精神运动活动和昼夜节律的节奏至关重要。鉴于在抑郁症和其他情绪障碍患者中看到这些不同领域异常的程度，对这些食用电路的关注是有意义的。确实，我们获得了本应用中提供的大量证据，因为这些食用电路在抑郁症动物模型中的重要性。该中心被组织成一个小的协调核心，两个科学核心和五个项目。转基因核心负责为中心调查人员提供最先进的分子工具，而行为核心负责为各个项目提供与情绪和动机有关的小鼠和大鼠的行为测试极为广泛的行为测试。项目1专注于转录因子CREB，作为食欲电路的关键调节及其在情绪和动机中的作用。随后的项目评估了这些神经途径中的一系列其他分子信号，这些信号既是CREB功能的重要调节剂，又是介导CREB行为表型的重要效应子。项目2专注于BDNF；项目3侧重于三种下丘脑肽，MSH，Orexin（phypocretin）和MCH；项目4专注于NPAS2和其他昼夜节律基因；项目5侧重于RGS蛋白，特别是RGS9和RGS16。