CSIA-Center for the Study of Impulsivity in Addiction

描述(申请人提供)：药物滥用和肥胖是我们国家最严重的两个健康问题，它们是具有相似的行为和神经生物学机制的成瘾形式。这项拟议的跨学科和转化性研究的目标是用创新的行为和神经成像方法检查导致肥胖的可卡因滥用和暴饮暴食障碍(BED)。据推测，冲动是这两种成瘾的主要因素，而大脑中主要的抑制性神经递质GABA在成瘾个体中减少。拟议中的成瘾冲动性研究中心(CSIA)将专注于成瘾倾向和抵抗者的冲动行为、GABA系统和神经成像。两个临床项目，涉及可卡因滥用者和卧床患者(和对照组)，一个使用药物滥用关键阶段动物模型的临床前部分，以及三个核心(神经成像、神经认知和管理)将组成CSIA。该中心将使用创新的动物模型来实施转换方法，这些模型预测易损性并测试与GABA相关的治疗，以向人类研究提供控制成瘾行为的关键变量的知识。我们在磁共振(MR)成像和行为测量方面的专业知识将是该中心的临床前和临床优势。具体目标包括：1)检查冲动行为，因为它预测(临床前)和(临床)可卡因滥用和床上的相关性，以及它与甜食偏好的衡量标准有关，因为甜味倾向预测药物滥用，与冲动相关，并可能是一种有用的预测和诊断工具。2)研究GABA水平和脑白质异常在与冲动和成瘾行为相关的脑区中的作用。3)使用行为学、磁共振成像和神经生物学技术(例如，GABA选择性治疗药物)来研究成瘾行为(滥用可卡因和暴饮暴食)之间的共性，从而可能导致干预策略。4)为了使用磁共振成像，包括用于观察白质异常的扩散张量成像(DTI)和揭示神经化学状态(尤其是GABA)的波谱(MRS)，以及成瘾倾向组和对照组的成像结果的差异，以及不同成瘾易感表型的大鼠将在类似的冲动性测试和成像程序中进行比较。5)比较男性和女性在所有指标上的结果，因为越来越多的证据表明，在成瘾行为方面存在性别差异。6)为了在NIDA资助的研究人员之间现有的合作关系和科学专业知识的基础上，拟议的合作将为预测、预防和治疗导致肥胖的药物滥用和床上疾病提供一站式的翻译努力。相关性：拟议的中心将提高我们对抑制控制的神经生物学的理解，这将导致预防和治疗成瘾障碍的新方法。

DESCRIPTION (provided by applicant): Drug abuse and obesity, two of our nation's most serious health concerns, are forms of addiction that share similar behavioral and neurobiological mechanisms. The goal of the proposed interdisciplinary and translational research is to examine cocaine abuse and binge eating disorder (BED) that leads to obesity with innovative behavioral and neuroimaging methodology. It is hypothesized that impulsivity is a major factor in these two forms of addiction, and GABA, the major inhibitory neurotransmitter in the brain, is reduced in addicted individuals. The proposed Center for the Study of Impulsivity in Addiction (CSIA) will focus on impulsive behavior, the GABA system, and neuroimaging in addiction-prone and -resistant individuals. Two clinical projects, involving cocaine abusers and BED patients (and controls), a preclinical component using animal models of critical phases of drug abuse, and three cores (neuroimaging, neurocognitive, and administrative) will comprise the CSIA. The Center will implement a translational approach using innovative animal models that predict vulnerability and test a GABA-related treatment to inform human studies with knowledge of key variables controlling the addictive behaviors. Our expertise with magnetic resonance (MR) imaging and behavioral measurements will be preclinical and clinical strengths of the Center. Specific aims include: 1) To examine impulsive behavior as it predicts (preclinical) and correlates with (clinical) cocaine abuse and BED and as it relates to measures of sweet preference, as a proclivity for sweet tastes predicts drug abuse, covaries with impulsiveness, and may be a useful predictive and diagnostic tool. 2) To investigate the role of GABA levels and white matter abnormalities in regions of the brain that is associated with impulsivity and addictive behavior. 3) To study commonalities among addictive behaviors (cocaine abuse and binge eating) using behavioral, MR imaging, and neurobiological techniques (e.g., GABA selective treatment drugs) that may lead to strategies for intervention. 4) To use MR imaging, both diffusion tensor imaging (DTI) to observe white matter abnormalities, and spectroscopy (MRS) that reveal neurochemical status, particularly GABA, and how imaging results differ in addiction-prone vs. controls, and rats with different addiction-vulnerable phenotypes will be compared on similar impulsivity tests and imaging procedures. 5) To compare results on all measures in males and females, as increasing evidence indicates sex differences in addictive behavior. 6) To build upon existing collaborative relationships and scientific expertise among NIDA-funded investigators the proposed collaboration will offer bench-to bedside, translational efforts for the prediction, prevention, and treatment of drug abuse and BED leading to obesity. RELEVANCE: The proposed center should improve our understanding of the neurobiology of inhibitory control, which will lead to new approaches for prevention and treatment for addictive disorders.