Mouse Model of Ethanol Relapse Propensity

乙醇复发倾向的小鼠模型

• 批准号: 7143960
• 负责人: ROBERTO I MELENDEZ
• 金额: $ 20.99万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7143960
• 关键词: alcoholism /alcohol abuse; behavioral /social science research tag; dopamine; ethanol; glutamates; high performance liquid chromatography; laboratory mouse; microdialysis; microinjections; model design /development; neuropsychology; neurotransmitter transport; nucleus accumbens; prefrontal lobe /cortex; psychological models; relapse /recurrence; sensory deprivation; substance abuse related behavior

DESCRIPTION (provided by applicant): Alcohol addiction continues to be a substantial medical, social, and financial problem in the United States. The dynamic process of alcohol addiction involves a transition from recreational alcohol use and deteriorates over time into excessive or compulsive drinking. Given that alcoholism is a chronic relapsing disease, it is not uncommon for many alcoholics to experience periods of drinking followed by periods of abstinence. This cyclic pattern of alcohol intake and deprivation may have severe consequnces on drinking behavior, including excessive or 'binge-like' consumption. There is very little pre-clinical information on the environmental and biological factors that mediate relapse-like alcohol drinking. Most basic reasearch using animal models has concentrated on the initiation and maintenance phases of alcohol intake. However, alcohol cosumption data (limited or continous access) by such approaches shows little variation over time (i.e., stable patterns of alcohol intake), thus fails to capture a fundamental characteristic of the addiction process. Thus, a goal has been to develop behavioral models that reflect the transition from controlled alcohol use to excessive consumption. A primary experimental approach to study relapse-like drinking has been through the expression of the alcohol deprivation effect (ADE), which is measured by an increase in alcohol intake and preference over baseline drinking conditions after a period of abstinence. The focus and overall objective of this proposal is to is employ a C57BL/6 model of repeated alcohol deprivations and relapse-like drinking to identify the neurobiological events that contribute to relapse. Conceivably, changes in extracellular glutamate levels the prefrontal cortex and ventral striatum may represent key neural substrates and neurochemical events critical in mediating relapse drinking behavior. To date, there is very little information available about changes in glutamatergic transmission that may relate to alcohol relapse. Therefore, a unique and novel feature of this proposal is to combine a robust C57BL/6 model of alcohol relapse drinking with in vivo microdialysis and site specific microinjections to validate the relevance of glutamatergic alterations in the prefrontal-ventral striatal pathway. Research to this end could potentially lead to pharmacotherapies that might reduce relapse risk and craving states.

描述（由申请人提供）：在美国，酒精成瘾仍然是一个实质性的医疗，社会和财务问题。 酒精成瘾的动态过程涉及从休闲饮酒的过渡，随着时间的流逝而恶化到过度或强迫性饮酒。鉴于酒精中毒是一种慢性复发疾病，因此许多酗酒者经历饮酒期并不少见。这种循环的酒精摄入量和剥夺模式可能会在饮酒行为上具有严重的结论，包括过度或“暴饮暴食”的消费。关于介导类似复发的饮酒的环境和生物学因素的临床前信息很少。使用动物模型的大多数基本搜索都集中在酒精摄入的启动和维护阶段。但是，通过这种方法，酒精的宇宙吸收数据（有限或连续访问）显示，随着时间的流逝，酒精摄入量的稳定模式几乎没有变化，因此无法捕获成瘾过程的基本特征。因此，目标是开发反映从受控酒精使用到过度消费的过渡的行为模型。研究类似复发的饮酒的主要实验方法 通过表达酒精剥夺效应（ADE），这是通过禁欲后的酒精摄入量增加和对基线饮用条件的偏好来衡量的。该提案的重点和整体目标是采用C57BL/6的重复饮酒和类似复发的饮酒模型来识别有助于复发的神经生物学事件。可以想象，细胞外谷氨酸水平的变化前额叶皮层和腹侧纹状体可能代表关键的神经底物，而神经化学事件对于介导复发饮用行为至关重要。迄今为止，几乎没有关于可能与酒精复发有关的谷氨酸能传播变化的信息。因此，该提案的独特而新颖的特征是将强大的C57BL/6醇复发饮用的模型与体内微透析和特定于位置的微型注射相结合，以验证前额叶 - 腹膜前纹状体途径中谷氨酸能改变的相关性。对此目的的研究可能会导致药物治疗，从而减少复发风险和渴望状态。