The Center of Excellence in Addiction Studies (CEAS)

成瘾研究卓越中心 (CEAS)

• 批准号: 10270346
• 负责人: Frank Porreca
• 金额: $ 128.9万
• 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/10270346
• 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; Structure; 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卓越中心（CEAS），提供核心服务， 用户开发项目，将导致新的研究成瘾。成瘾和复发的特征是 大脑回路失调，涉及大脑奖励回路活动减少，反应性增加 压力回路和执行皮层回路功能受损。在基底节中观察到神经变化 神经节，杏仁核和前额叶皮质区，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（CRF）， 强啡肽、谷氨酸盐和其他物质。虽然慢性疼痛和成瘾是不同的疾病，但有一个显着的 滥用药物和慢性疼痛对这些回路的影响之间存在重叠。我们的教师有广泛的 在评估机制的专业知识，这些电路的疼痛促进适应不良的基础。的 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 这些结构要素将使CEAS有效运作。神经回路的遗传靶向 Core将允许用户使用包括CRISPR/Cas9基因编辑在内的尖端遗传技术， 化学遗传学和光遗传学，以产生细胞和电路特异性操作， 与成瘾有关的机制。神经分析核心将为用户提供先进的方法， 以毫秒到数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： 使用行为测定法评价成瘾过程（包括成瘾药物的影响）的成瘾 对认知功能的影响CEAS的调查人员已经合作多年，并分享了 个人研究经费。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、北方亚利桑那大学、新墨西哥州大学和 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了西南地区 从事成瘾科学研究。CEAS将通过招募新的研究人员， 来自神经科学和成瘾领域代表性不足人群的研究人员和学生。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。此外该 来自CEAS的资金的影响将通过亚利桑那大学的匹配资金的承诺而扩大 以及最近成立的疼痛和成瘾综合中心。CEAS将提供关键 为用户提供符合NIDA目标的服务，以加强成瘾研究， 开发可以阻止阿片类药物流行并影响其他药物滥用的疗法 紊乱核心之间的密切合作确保了成瘾所有领域的高专业知识 研究，并将允许强调科学严谨性和可重复性的结果测量。