A Preclinical Model of Adolescent Toluene Abuse in Rats

大鼠青少年甲苯滥用的临床前模型

• 批准号: 6876795
• 负责人: SCOTT E BOWEN
• 金额: $ 21.38万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6876795
• 关键词: adolescence (12-20); age difference; brain metabolism; brain morphology; disease /disorder model; drug administration rate /duration; drug metabolism; gender difference; inhalation drug abuse; laboratory rat; magnetic resonance imaging; model design /development; neurochemistry; neurotoxicology; nuclear magnetic resonance spectroscopy; psychopharmacology; toluene

DESCRIPTION (provided by applicant): This R21 application is in response to NIDA RFA #DA-04-011 "Animal Models of Adolescent Drug Abuse: Integrative Studies of Brain and Behavioral Development." Inhalant abuse is a significant public health problem throughout the U.S. and the world. Adolescents are by far the largest population of solvent abusers, particularly of toluene-based products. Consequently, there is special concern about the negative impact that adolescent inhalant abuse can have on life-long behavioral and cognitive maturation. Yet, there is a relative paucity of systematic studies of the developmental consequences of adolescent binge exposure to inhaled organic solvents. The clinical picture of adolescent inhalant abuse may be confounded by use of multiple solvents, exposure to other drugs, and maturational and environmental variables. An initial goal of the proposed research is to develop a rodent model of adolescent inhalant abuse, using our established model of clinically relevant abuse patterns of inhalant exposure, to assess behavioral and neurochemical effects. A key strength of this proposal is the use of our preclinical model of inhalant administration that mimics the repeated, brief, episodic, high-dose exposure pattern in humans who abuse toluene and other solvents. We will characterize, in rats, behavioral, neurobiological, and psychopharmacological consequences of adolescent binge exposure to inhaled organic solvents during defined "critical periods" of postnatal development that mirror maturational stages of human development: juveniles, adolescents, young adults and adults. We will examine the developmental profiles of behavioral and neurochemical sensitivity to toluene. The proposed study will include behavioral assessments (e.g., motor function and learning) and state-of-the-art brain imaging techniques. These include T-2 weighted magnetic resonance imaging (MRI) scans to measure regional changes in brain size, and high-resolution "magic-angle" -spin proton magnetic resonance spectroscopy (HR-MAS 1H-MRS) at 11.7 Tesla (T), i.e., a very powerful magnetic field, to examine the age-dependent effects of toluene exposure on neurochemistry. Finally, this research will generate a clinically relevant model with which neuroanatomical and biochemical outcomes, along with the mechanisms of adolescent inhalant abuse may be studied. The model also has the potential to assist in devising effective treatments and prevention strategies for adolescent inhalant abuse.

描述（由申请人提供）：此R21申请是对NIDA RFA＃DA-04-011的响应，“青少年药物滥用的动物模型：大脑和行为发展的综合研究”。 吸入式滥用是美国和世界各地的一个重大公共卫生问题。青少年是迄今为止最大的溶剂滥用者，特别是基于甲苯的产品。 因此，人们特别关心青少年吸入式虐待对终身行为和认知成熟的影响。 然而，对于吸入有机溶剂的青少年暴饮暴食的发育后果，系统研究相对匮乏。 使用多种溶剂，接触其他药物以及成熟和环境变量，青少年吸入式滥用的临床情况可能会混淆。 拟议的研究的最初目标是使用我们既定的吸入式滥用模式的吸入式滥用模型来开发一种啮齿动物模型，以评估行为和神经化学效应。 该提案的一个关键优势是使用我们的吸入式给药模型，这些模型模仿了滥用甲苯和其他溶剂的人类中重复，简短，情节性的高剂量暴露模式。 我们将在大鼠，行为，神经生物学和心理药物学的后果中表征青少年暴露在定义的“关键时期”中吸入的有机溶剂的后果，这反映了人类发展的成熟阶段：少年，青少年，年轻人，成人和成人。 我们将研究行为和神经化学对甲苯敏感性的发育概况。 拟议的研究将包括行为评估（例如运动功能和学习）以及最先进的脑成像技术。 其中包括T-2加权磁共振成像（MRI）扫描以测量脑大小的区域变化，以及高分辨率的“魔法” - 旋转质子磁共振光谱（HR-MAS 1H-MRS）在11.7 tesla（T）（即T），即非常强大的磁场，以检查耐受性epportion的耐受性eptistion的效果。 最后，这项研究将产生与临床相关的模型，可以研究神经解剖学和生化结果，以及青少年吸入式滥用的机制。 该模型还有可能协助制定有效的治疗和预防策略，以供青少年滥用。