The Center of Excellence in Addiction Studies (CEAS)

成瘾研究卓越中心 (CEAS)

基本信息

批准号：
10626079
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
项目类别：
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/10626079
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 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 Leadership Learning Letters Link Measurement Measures Mediator 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 Phase II Clinical Trials Physicians Pilot Projects Population Prefrontal Cortex 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 Underrepresented Students 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 motivated behavior negative affect neural neural circuit neurochemistry novel strategies operation opioid epidemic opioid use opioid withdrawal optogenetics prevent recruit stem temporal measurement therapy development translational approach treatment strategy

项目摘要

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），该中心将提供核心服务，使用户开发将导致成瘾新研究的项目。成瘾和复发的特点是大脑回路失调，涉及大脑奖励回路活动减少、反应能力增加压力回路和执行皮层回路功能受损。在基础神经元中观察到变化神经节、扩展的杏仁核和前额皮质区域，并涵盖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、谷氨酸等。虽然慢性疼痛和成瘾是不同的疾病，但有一个显着的特征滥用药物和慢性疼痛对这些回路的影响之间存在重叠。我们的师资力量广泛评估这些回路中的疼痛所促进的适应不良的机制的专业知识。这 CEAS 将由四个核心和一个试点研究项目组成。行政核心将提供使 CEAS 有效运作的结构要素。神经回路的基因靶向 Core 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产生细胞和电路特异性操作来评估潜力与成瘾相关的机制。神经分析核心将为用户提供先进的方法以毫秒到天的时间分辨率和空间特异性来测量神经递质通过先进的检测手段。行为核心将允许用户探索相关问题使用行为分析来评估成瘾过程，包括成瘾药物的影响关于认知功能。 CEAS 的研究人员已经合作多年，并分享和个人研究经费。此外，CEAS 将为大学的其他研究人员提供机会亚利桑那大学以及亚利桑那州立大学、北亚利桑那大学、新墨西哥大学和德克萨斯理工大学拉伯克和埃尔帕索健康科学中心建立西南地区从事成瘾科学。 CEAS 将通过招募人员来促进成瘾研究的多样性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 将利用现有资金开展成瘾研究的新研究。此外， CEAS 资金的影响将通过亚利桑那大学配套资金的承诺而放大以及最近成立的疼痛和成瘾综合中心。 CEAS将提供关键向用户提供符合 NIDA 加强成瘾研究目标的服务，其目标是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失调。核心之间的密切合作确保了成瘾各个领域的高度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衡量。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury.

血管紧张素-(1-7) 可改善轻度脑外伤小鼠的认知功能并减少炎症。

DOI：
发表时间：
2022
期刊：
影响因子：
0
作者：
Bruhns, Ryan P;Sulaiman, Maha Ibrahim;Gaub, Michael;Bae, Esther H;Davidson Knapp, Rachel B;Larson, Anna R;Smith, Angela;Coleman, Deziree L;Staatz, William D;Sandweiss, Alexander J;Joseph, Bellal;Hay, Meredith;Largent;Vanderah
通讯作者：
Vanderah

Decreased dopaminergic inhibition of pyramidal neurons in anterior cingulate cortex maintains chronic neuropathic pain.

前扣带皮层锥体神经元的多巴胺能抑制减少维持慢性神经性疼痛。