Interactions of Stress and Nicotine

压力和尼古丁的相互作用

• 批准号: 7195028
• 负责人: JOSHUA A BERMAN
• 金额: $ 17.31万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7195028
• 关键词: Acute; Affective; Award; Behavior; Behavioral; Biology; Brain; Cholinergic Agents; Chronic; Chronic stress; Clinical; Collaborations; Condition; Dependence; Development; Disease; Exposure to; Gene Activation; Gene Expression; Genes; Glutamates; Goals; Immediate-Early Genes; Investigation; K-Series Research Career Programs; Lead; Learning; Link; Location; Mediating; Mentors; Molecular; Molecular Biology; Molecular Neurobiology; Mood Disorders; Neurons; Nicotine; Nicotine Dependence; Nucleus Accumbens; Pathway interactions; Pattern; Pharmaceutical Preparations; Phase; Play; Process; Regulation; Research; Rewards; Role; Scientist; Stimulus; Stress; System; Testing; Time; Training; Ventral Tegmental Area; addiction; biological adaptation to stress; career; cholinergic; design; dosage; drug craving; drug of abuse; gene induction; hedonic; interest; mouse model; neurochemistry; neurotransmission; novel; programs; response

DESCRIPTION (provided by applicant): Stress and affective dysregulation play an important role in the course of addiction to nicotine and in the course of addictive disorders in general. A better understanding of how stress and hedonic systems interact is critical to developing better treatments for these conditions. Chronic nicotine and stress may cause an overlapping network of changes in neuronal function and gene expression which over time may render the brain more vulnerable to stress, stress-induced drug craving, and drug effects. The research goals of this Mentored Clinical Scientist Career Development Award are to understand relationships between changes in neuronal activity and gene expression induced by stress and by nicotine, to locate these changes precisely in neuroanatomical circuits, and to correlate such changes with steps in drug-taking in a mouse model. The application emphasizes understanding anatomical patterns because such an approach could suggest new brain locations and neurochemical targets for novel treatments for nicotine addiction and addictive disorders in general. The first aim of the program is to understand how chronic exposure to stress alters responses to nicotine at the level of neuronal activation. The second aim is to learn in greater detail where and to what extent nicotine and stress act in similar ways in the brain, focusing on patterns of gene expression. The final portion of the program seeks to understand how stress may potentiate nicotine's ability to regulate gene expression in the brain in ways that are relevant to the addictive process. Three distinguished mentors will be responsible for the career development of the candidate during the award period - Dr. Loma Role, an expert in molecular neurobiology and biology of cholinergic systems; Dr. Eliot Gardner, an expert in the biology of addictions; and Dr. Alexander Glassman, who provides clinical expertise in nicotine addiction and mood disorders. The candidate has also arranged collaborations with other experts who will add to the training component and help accomplish the research. These are Dr. Patrick Hof, an expert neuroanatomist; Dr. David Talmage and Dr. Etienne Sibille, experts in molecular biology and use of microarrays; Dr. Jay Gingrich, an expert behavioral neuroscientist; and Dr. Frances Levin, an additional clinical expert on addiction studies. The program has been designed to culminate in the candidate establishing an independent research program.

描述（由申请人提供）： 压力和情感失调在尼古丁成瘾过程和一般成瘾性疾病过程中起着重要作用。更好地理解压力和享乐系统如何相互作用对于开发更好的治疗方法至关重要。慢性尼古丁和压力可能会导致神经元功能和基因表达变化的重叠网络，随着时间的推移，可能会使大脑更容易受到压力、压力引起的药物渴望和药物效应的影响。 该导师临床科学家职业发展奖的研究目标是了解压力和尼古丁引起的神经元活动和基因表达变化之间的关系，在神经解剖回路中精确定位这些变化，并将这些变化与吸毒步骤相关联在小鼠模型中。该应用程序强调了解解剖学模式，因为这种方法可以为尼古丁成瘾和成瘾性疾病的新疗法提出新的大脑位置和神经化学靶标。 该计划的首要目标是了解长期暴露在压力下如何改变神经元激活水平对尼古丁的反应。第二个目标是更详细地了解尼古丁和压力在大脑中以相似方式起作用的位置和程度，重点关注基因表达模式。该项目的最后部分旨在了解压力如何增强尼古丁以与成瘾过程相关的方式调节大脑中基因表达的能力。 三位杰出导师将负责候选人在颁奖期间的职业发展——分子神经生物学和胆碱能系统生物学专家Loma Role博士；艾略特·加德纳博士，成瘾生物学专家；亚历山大·格拉斯曼 (Alexander Glassman) 博士提供尼古丁成瘾和情绪障碍方面的临床专业知识。候选人还安排了与其他专家的合作，这些专家将增加培训内容并帮助完成研究。他们是帕特里克·霍夫 (Patrick Hof) 博士，一位神经解剖学专家； David Talmage 博士和 Etienne Sibille 博士，分子生物学和微阵列应用方面的专家； Jay Gingrich 博士，行为神经科学家专家；弗朗西斯·莱文博士是成瘾研究的另一位临床专家。该计划旨在最终让候选人建立一个独立的研究计划。