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.

我们建议建立成瘾研究卓越中心（CEAS），该中心将提供允许的核心服务 用户开发将导致成瘾新研究的项目。成瘾和复发的特征是 脑电路的失调，涉及大脑奖励电路活性减少，反应性提高 压力电路和执行皮层电路功能受损。在基础上观察到神经变化 神经节，延伸的杏仁核和前额叶皮质区域，包括广泛的内源性 神经递质，包括多巴胺，阿片类肽，内源性大麻素，皮质激素释放因子（CRF）， Dynorphin，谷氨酸和其他人。慢性疼痛和成瘾是不同的疾病，但有一个了不起的 滥用药物和慢性疼痛对这些电路的影响之间的重叠。我们的教师有广泛的 评估这些电路中疼痛促进的疾病的机制评估的专业知识。这 CEA将由四个核心和一个试点研究项目组成。行政核心将提供 结构元素将允许CEAS有效运作。神经回路的遗传靶向 核心将允许用户采用尖端遗传技术，包括CRISPR/CAS9基因编辑， 化学遗传学和光遗传学以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高级方法 测量具有毫米秒至几天且空间特异性的时间分辨率的神经递质 通过高级检测方法。行为核心将允许用户探索与 使用行为测定的成瘾，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了多年，并分享了 个人研究资金。此外，CEAS将为大学的其他调查人员提供机会 亚利桑那州以及亚利桑那州立大学，北亚利桑那大学，新墨西哥大学和 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。 CEAS将通过招募来促进成瘾研究中的多样性 来自代表性不足的神经科学和成瘾人群的调查人员和学生。的影响 CEA将利用既定的资金来开发成瘾研究的新研究。另外， 来自CEAS的资金的影响将通过亚利桑那大学的资金的承诺来扩大 以及最近建立的疼痛和成瘾中心。 CEAS将提供钥匙 与NIDA目标相对应的用户的服务，以增强成瘾研究的目标 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 疾病。核心之间的密切合作确保了成瘾的所有领域的高专业知识 研究并将允许强调科学严格和可重复性的结果措施。