Addiction and the Neuropharmacology of Psychostimulants

成瘾和精神兴奋剂的神经药理学

• 批准号: 7668611
• 负责人: Kathryn A. Cunningham
• 金额: $ 11.71万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7668611
• 关键词: Accounting; Addictive Behavior; Amphetamines; Animal Model; Anxiety; Area; Behavioral; Biological; Biological Markers; Biological Process; Brain; Chronic; Chronic stress; Clinical Trials; Cocaine; Cocaine Dependence; Complex; Detection; Development; Diagnostic; Disease; Dopamine; Drug Addiction; Drug abuse; Drug usage; Drug user; Educational Curriculum; Etiology; Exposure to; Funding; Genes; Goals; Grant; Health Professional; Immunohistochemistry; Individual; Investigation; Leadership; Ligands; Mediating; Medical; Mentors; Methods; Microinjections; Modeling; Molecular; Motor Activity; National Institute of Drug Abuse; Neurobiology; Neuropharmacology; Nucleus Accumbens; Pathway interactions; Pharmaceutical Preparations; Pharmacology; Phenotype; Physiological; Prefrontal Cortex; Process; Protein Analysis; Proteins; Proteomics; Psychostimulant dependence; Relapse; Research; Research Design; Resolution; Role; Scientist; Self Administration; Serotonin; Serotonin Receptor 5-HT2A; Serum; Staging; Stimulus; Stress; Structure; Symptoms; System; Technology; Testing; Texas; Training; Translational Research; Treatment outcome; Universities; Ursidae Family; Ventral Tegmental Area; addiction; affective psychoses; base; biological adaptation to stress; career; college; craving; depression; dopamine system; dopamine transporter; drug of abuse; drug seeking behavior; ecstasy; experience; in vivo; neurobehavioral; neurochemistry; neuronal cell body; neurotransmission; preference; professor; prognostic; programs; protein profiling; psychostimulant; receptor; relating to nervous system; response; stimulant abuse; success; tool

DESCRIPTION (provided by applicant): The Candidate, Kathryn A. Cunningham, has been supported by a K02 (DA00260) from 5/1/96-4/30/05, a period marked by a number of career, research and mentoring successes. The PI is the Chauncey Leake Distinguished Professor in Pharmacology at the University of Texas Medical Branch (UTMB), is the Director of the UTMB Center for Addiction Research and Director of a NIDA training grant. Continuously funded by NIDA, she has been active in drug abuse research for 20 years and has made important contributions to the field in areas related to both the neurobiology of abused drugs and addictive processes. Her current research endeavors are focused on gaining a more complete understanding of the neural basis underlying the effects of cocaine and the substituted amphetamine 3,4-methylenedioxymethamphetamine (MDMA) which share actions to stimulate brain serotonin (5-HT) systems. Serotonin is involved in the etiology of psychotic and affective disorders (e.g., anxiety, depression) which are often experienced by drug users and the 5-HT system is an important target in the quest for medications for addiction. Accordingly, the research goals of the present application for a K05 will include tests of the following hypotheses: (1) the oppositional roles of 5-HT2A receptors (5- HT2AR) and 5-HT2CR to control the cellular and behavioral responses to cocaine occur within the mesocorticoaccumbens circuit; models of addictive behavior (conditioned place preference, self-administration), high resolution immunohistochemistry and localized microinjection of receptor-specific ligands and virally-mediated genes are being employed [DA 06511]; (2) the in vivo effects of MDMA are mediated by both concurrent and sequential activation of 5- HT and dopamine systems; behavioral pharmacological and molecular biological tools are being used to dissect the roles of these systems [DA 13595]; (3) vulnerability to drug self-administration is related to the protein profile of the chronic stress response in brain; proteomics approaches are being employed to assess this hypothesis [DA 0 16905]. With the current proposal for a K05, these research goals will be supplemented by the development of expertise and the application of emerging proteomics technologies to characterize key proteins and protein signatures associated with exposure to abused drugs in animal models of addiction and in vulnerability to drug dependence. A related long term goal is to expand our program via collaborative interactions to include translational investigations in the identification of serum biomarkers of addiction phenotypes to allow detection of the disease at earliest stage of progression (diagnostic) and biomarkers of the disease stage in an addict to foretell disease and treatment outcome (prognostic). The mentoring goals will be to provide guidance for junior scientists in transdisciplinary investigations in addiction research, to continue to administer the NIDA training grant [DA07287] and to develop curricula for the training of health care professionals in the sciencebased treatment of drug dependence. The leadership goals include creation and direction of the University of Texas Medical Branch (UTMB) Center for Addiction Research, continued involvement in research initiatives in drug abuse at UTMB, in Texas and the U.S., and active participation in the leadership of the College on Problems of Drug Dependence.

描述（由申请人提供）： 候选人凯瑟琳·坎宁安（Kathryn A. Cunningham）在5/1/1/96-4/30/05的K02（DA00260）支持下，这是许多职业，研究和指导成功的时期。 PI是德克萨斯大学医学分公司（UTMB）的Chauncey Leake杰出教授，是UTMB成瘾研究中心的主任，也是NIDA培训补助金的主任。她不断由NIDA资助，活跃于药物滥用研究已有20年了，并在与滥用药物的神经生物学和成瘾过程有关的领域为该领域做出了重要贡献。她目前的研究努力集中在获得对可卡因和取代的苯丙胺3,4-甲基二甲基甲甲基苯丙胺（MDMA）影响的神经基础上的更全面了解，这些苯丙胺（MDMA）共同刺激刺激脑血清素（5-HT）系统的作用。 5-羟色胺参与了药物使用者通常经历的精神病和情感障碍（例如焦虑，抑郁症）的病因，而5-HT系统是追求成瘾药物的重要目标。因此，本申请的研究目标将包括以下假设的测试：（1）5-HT2A受体（5- HT2AR）和5-HT2CR的对立作用，以控制对可卡因的细胞和行为反应，在中皮层中发生的可卡因；正在使用成瘾行为（条件地位偏好，自我管理），高分辨率免疫组织化学以及受体特异性配体的局部微注射和病毒介导的基因[DA 06511]； （2）MDMA的体内效应是由5-HT和多巴胺系统的并发和顺序激活介导的；行为药理和分子生物学工具被用于剖析这些系统的作用[DA 13595]； （3）对药物自我给药的脆弱性与大脑慢性应激反应的蛋白质谱有关；正在采用蛋白质组学方法来评估这一假设[DA 0 16905]。有了当前关于K05的建议，这些研究目标将通过专业知识的发展以及新兴蛋白质组学技术的应用来补充，以表征与在成瘾动物模型中与滥用药物相关的关键蛋白质和蛋白质特征，并易于药物依赖性。一个相关的长期目标是通过协作互动扩展我们的计划，以在鉴定成瘾表型的血清生物标志物中进行翻译研究，以允许在进展的最早（诊断）（诊断）和疾病阶段的生物标志物中检测到该疾病阶段的生物标志物，以使瘾君子对预甲疾病疾病和治疗结果（预后）。指导目标是为成瘾研究中的跨学科研究提供指导，以继续管理NIDA培训赠款[DA07287]，并开发课程，以培训医疗保健专业人员在基于科学的药物依赖治疗中。领导目标包括德克萨斯大学医学分支（UTMB）成瘾研究中心的创建和指导，继续参与UTMB，德克萨斯州和美国的药物滥用研究计划，以及积极参与吸毒问题的大学领导。