The Center of Excellence in Addiction Studies (CEAS)

成瘾研究卓越中心 (CEAS)

• 批准号: 10469424
• 负责人: Frank Porreca
• 金额: $ 134.68万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10469424
• 关键词: Acute; Acute Pain; Addictive Behavior; Address; Amygdaloid structure; Animals; Anxiety; Applications Grants; Area; Arizona; Basal Ganglia; Behavioral; Behavioral Assay; Biology; Brain; Brain region; CRISPR/Cas technology; Cells; Chemicals; Cholecystokinin; Clinical; Cognition; Cognitive; Collaborations; Complement; Corpus striatum structure; Corticotropin-Releasing Hormone; Data; Development; Disease; Dopamine; Dynorphins; Education; Elements; Endocannabinoids; Ensure; Evaluation; Event; Executive Dysfunction; Faculty; Funding; Future; Genes; Genetic; Genetic Techniques; Glutamates; Goals; Health Professional; Health Sciences; Impairment; Impulsive Behavior; Impulsivity; Individual; Lead; Leadership; Letters; Link; Measurement; Measures; Mediator of activation protein; Methods; Modernization; Molecular; Molecular Target; Motivation; Mus; National Institute of Drug Abuse; Negative Reinforcements; Neurosciences; Neurotransmitters; New Mexico; Nucleus Accumbens; Opioid; Opioid Antagonist; Opioid Peptide; Outcome; Outcome Measure; Pain; Pain Clinics; Pain Research; Pain management; Patients; Persistent pain; Pharmaceutical Preparations; Phase; Physicians; Pilot Projects; Population; Process; Program Research Project Grants; Public Health; Rattus; Relapse; Reproducibility; Research; Research Personnel; Research Project Grants; Research Support; Resolution; Rewards; Science; Secure; Services; Signal Transduction; Specificity; Standardization; Strategic Planning; Stress; Students; Substance Addiction; Substance abuse problem; System; Techniques; Texas; Underrepresented Populations; United States; United States National Institutes of Health; Universities; Withdrawal; Work; addiction; base; biological adaptation to stress; brain circuitry; chronic pain; cognitive function; detection method; drug addiction therapy; drug of abuse; drug reinforcement; drug relapse; executive function; flexibility; frontal lobe; insight; kappa opioid receptors; millisecond; negative affect; neural circuit; neurochemistry; novel strategies; operation; opioid epidemic; opioid use; opioid withdrawal; optogenetics; prevent; ranpirnase; recruit; relating to nervous system; stem; temporal measurement; therapy development; translational approach; treatment strategy

We propose to establish a Center of Excellence for Addiction Studies (CEAS) that will offer core services allowing users to develop projects that will lead to new research in addiction. Addiction and relapse are characterized by dysregulation of brain circuitry that involves diminished activity of brain reward circuits, increased responsiveness of stress circuits and impaired functioning of executive cortical circuits. Neural changes are observed in the basal ganglia, extended amygdala and prefrontal cortical regions and encompass a wide range of endogenous neurotransmitters including dopamine, opioid peptides, endocannabinoids, corticotropin releasing factor (CRF), dynorphin, glutamate and others. While chronic pain and addiction are different disorders, there is a remarkable overlap between the influence of drugs of abuse and chronic pain on these circuits. Our faculty has broad expertise in evaluation of mechanisms that underlie the maladaptations promoted by pain in these circuits. The CEAS will be composed of four Cores and a Pilot Research Project. The Administrative Core will provide the structural elements that will allow efficient functioning of the CEAS. The Genetic Targeting of Neural Circuits Core will allow users to employ cutting edge genetic techniques including CRISPR/Cas9 gene editing, chemogenetics and optogenetics to produce cell and circuit-specific manipulations to evaluate potential mechanisms relevant to addiction. The Neuroanalytical Core will provide users with advanced methods of measuring neurotransmitters with temporal resolution spanning milli-seconds to days and with spatial specificity through advanced detection methods. The Behavioral Core will allow users to explore questions relevant to addiction using behavioral assays that evaluate addictive processes including the influence of addictive drugs on cognitive function. Investigators in the CEAS have worked together for many years and have shared and individual research funding. Additionally, the CEAS will offer opportunities for other investigators at University of Arizona as well as Arizona State University, Northern Arizona University, The University of New Mexico and Texas Tech University Health Sciences Center at Lubbock and El Paso establishing a Southwestern region engaged in addiction sciences. The CEAS will promote increased diversity in addiction research by recruiting investigators and students from under-represented populations in neuroscience and addiction. The impact of the CEAS will be to leverage established funding to develop new research on addiction research. In addition, the impact of funds from the CEAS will be amplified by commitments of matching funds from the University of Arizona and from a recently established Comprehensive Center of Pain and Addiction. The CEAS will provide key services to its users that correspond with the goals of the NIDA to enhance addiction research with a goal of development of therapies that can stem the opioid epidemic as well as impacting other substance abuse disorders. The close collaboration between the Cores ensures high expertise in all areas of the addiction research and will permit outcome measures emphasizing scientific rigor and reproducibility.

我们建议建立一个成瘾研究英才中心(CEAS)，提供核心服务， 用户开发的项目将导致对成瘾的新研究。上瘾和复发的特征是 大脑回路调节失调，包括大脑奖赏回路活动减弱，反应性增强 压力回路和执行皮质回路功能受损。在基底节观察到神经变化。 神经节，延伸的杏仁核和前额叶皮质区域，并包括广泛的内源性 神经递质包括多巴胺、阿片肽、内源性大麻素、促肾上腺皮质激素释放因子、 强啡肽、谷氨酸等。虽然慢性疼痛和成瘾是不同的疾病，但有一个值得注意的 滥用药物和慢性疼痛对这些回路的影响之间存在重叠。我们的教职员工范围很广 在评估这些回路中疼痛促进的适应不良的机制方面的专业知识。这个 CEAS将由四个核心和一个试点研究项目组成。行政核心将提供 将使CEAS有效运作的结构要素。神经回路的基因靶向性研究 CORE将允许用户使用尖端基因技术，包括CRISPR/Cas9基因编辑， 化学遗传学和光遗传学产生细胞和电路特异性操作以评估潜力 与成瘾有关的机制。神经分析核心将为用户提供先进的 以从毫秒到几天的时间分辨率和空间特异性测量神经递质 通过先进的检测方法。行为核心将允许用户探索与以下内容相关的问题 使用行为分析评估成瘾过程，包括成瘾药物的影响 关于认知功能。CEAS的调查人员已经合作多年，并分享了 个人研究基金。此外，CEAS将为大学的其他研究人员提供机会 以及亚利桑那州立大学、北亚利桑那大学、新墨西哥大学和 位于拉伯克和埃尔帕索的德克萨斯理工大学健康科学中心建立西南地区 从事成瘾科学研究。CEAS将通过招募以下人员促进成瘾研究的多样性 研究人员和来自神经科学和成瘾领域代表性不足的人群的学生。经济衰退带来的影响 CEAS将利用现有的资金来开发关于成瘾研究的新研究。此外， 来自CEAS的资金的影响将被亚利桑那大学承诺的匹配资金放大 来自最近成立的综合疼痛和成瘾中心。CEAS将提供关键 为其用户提供符合NIDA目标的服务，以加强成瘾研究，目标是 开发可遏制阿片类药物流行并影响其他物质滥用的治疗方法 精神错乱。各中心之间的密切合作确保了成瘾所有领域的高水平专业知识 研究将允许采用注重科学严谨性和可重复性的成果衡量标准。