Neurobehavioral Regulation of Cigarette Cravings

香烟渴望的神经行为调节

• 批准号: 7257188
• 负责人: Brian L Hitsman
• 金额: $ 5.98万
• 依托单位: MIRIAM HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2008-03-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7257188
• 关键词: Abstinence; Acute; Affect; Affective; Behavioral; Blood; Brain; Carbon Monoxide; Catecholamines; Cigarette; Cues; Dependence; Diagnostic; Disinhibition; Doctor of Medicine; Doctor of Philosophy; Dopamine; Double-Blind Method; High Prevalence; Individual; Individual Differences; Investigation; Maintenance; Major Depressive Disorder; Measurement; Measures; Mediating; Mediator of activation protein; Mental Depression; Mentored Clinical Scientist Award; Modeling; Moods; National Institute of Drug Abuse; Neurobiology; Neurosciences; Neurotransmitters; Nicotine; Nicotine Dependence; Patients; Personal Satisfaction; Pharmaceutical Preparations; Pharmacological Treatment; Placebo Control; Plasma; Play; Price; Process; Property; Purpose; Range; Rate; Recurrence; Regulation; Relapse; Relative (related person); Research; Research Personnel; Research Training; Rewards; Risk; Role; Sampling; Science; Serotonin; Smoke; Smoker; Smoking; Smoking Behavior; Structure; Symptoms; System; Testing; Thinking; Time; Training; Tryptophan; Tyrosine; Universities; Withholding Treatment; alcohol research; alpha-Methyltyrosine; career; craving; depressive symptoms; design; desire; drug craving; drug reinforcement; dysphoria; experience; gamma-Aminobutyric Acid; medical schools; multidisciplinary; neurobehavioral; neurochemistry; nicotine craving; pre-clinical research; programs; psychobiologic; response; reward processing; smoking cessation; theories

DESCRIPTION (provided by applicant): This is a resubmission of a NIDA K08 Mentored Clinical Scientist Award. My career objective is to establish myself as independent investigator with a strong program of preclinical research focusing on the neurobiology of nicotine dependence and major depression. The application proposes a comprehensive, five-year program of supervised training and research with Raymond Niaura, Ph.D., and Lawrence H. Price, M.D., at Brown Medical School, and Marina Picciotto, Ph.D., and Tony P. George, M.D. at Yale School of Medicine. This multidisciplinary team will provide close guidance in a training plan comprised of structured didactics, seminars, and coursework in the Brown Brain Sciences Program and in the Department of Neuroscience at Yale University. The focus of the Research Plan is to characterize the neurobehavioral mechanisms that regulate cigarette cravings and smoking behavior among nicotine dependent individuals with and without vulnerability to major depression. In two double-blind, placebo-controlled challenge studies, acute tryptophan depletion (ATD) and alpha-methyl-para-tyrosine (AMPT) will be used to examine the effects of serotonin and dopamine depletion, respectively, on cravings and smoking topography. The specific aims are: (1) To examine the role of serotonin and dopamine in regulating cigarette cravings and smoking topography in depression vulnerable smokers; (2) To determine the relative effects of ATD and AMPT administration on individual differences in (obsessive craving, reward craving) and smoking topography; (3) To determine whether any changes in cue-induced cravings in response to ATD or AMPT administration correspond to changes in smoking topography; and (4) To explore whether associations among craving-related measures (e.g., obsessive and reward craving), smoking (e.g., topography, blood nicotine levels), and diagnostic group are mediated by changes in mood. Results of this research will increase understanding of the associations among serotonin and dopamine function, cue-induced cravings and vulnerability to major depression, and may have implications for tailoring pharmacological treatments to nicotine craving profiles.

描述（由申请人提供）： 这是 NIDA K08 指导临床科学家奖的重新提交。我的职业目标是使自己成为一名独立研究者，拥有强大的临床前研究计划，重点关注尼古丁依赖和重度抑郁症的神经生物学。该申请提出了一项为期五年的全面监督培训和研究计划，由布朗医学院的 Raymond Niaura 博士和 Lawrence H. Price 医学博士、Marina Picciotto 博士和 Tony P.乔治，耶鲁大学医学院医学博士。这个多学科团队将为培训计划提供密切指导，该计划包括布朗脑科学项目和耶鲁大学神经科学系的结构化教学、研讨会和课程作业。该研究计划的重点是确定尼古丁依赖者（无论是否易患重度抑郁症）调节香烟渴望和吸烟行为的神经行为机制。在两项双盲、安慰剂对照的挑战研究中，急性色氨酸消耗（ATD）和α-甲基对酪氨酸（AMPT）将分别用于检查血清素和多巴胺消耗对烟瘾和吸烟地形的影响。 具体目标是： (1) 研究血清素和多巴胺在调节易患抑郁症的吸烟者的香烟渴望和吸烟地形中的作用； (2) 确定 ATD 和 AMPT 给药对个体差异（强迫性渴望、奖赏性渴望）和吸烟地形的相对影响； (3) 确定 ATD 或 AMPT 给药引起的提示诱导烟瘾的任何变化是否与吸烟形态的变化相对应；和 (4) 探讨渴望相关指标（例如强迫性渴望和奖励渴望）、吸烟（例如地形、血液尼古丁水平）和诊断组之间的关联是否由情绪变化介导。 这项研究的结果将增进对血清素和多巴胺功能、提示诱发的渴望和重度抑郁症易感性之间关联的理解，并可能对针对尼古丁渴望特征定制药物治疗具有影响。