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Compensation of Nicotine Self-Administration

尼古丁自我给药的补偿

基本信息

批准号：
7273382
负责人：
ANDREW Charles HARRIS
金额：
$ 4.14万
依托单位：
HENNEPIN HEALTHCARE RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-11-01 至 2008-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Elucidating the mechanisms underlying compensation, or changes in smoking behavior that occur in response to decreased nicotine availability, is crucial for characterizing smoking reduction as an approach to managing tobacco dependence in smokers who are unwilling or unable to quit. Our laboratory has developed two rodent models of smoking reduction in which compensatory increases in nicotine selfadministration are observed following reductions in duration of daily nicotine access or nicotine dose per infusion. The current proposal will examine whether severity of the negative affective (i.e., emotional) consequences of nicotine withdrawal, as assessed by elevated intracranial self-stimulation thresholds, is predictive of compensation in either the dose or access models of reduction. Additional studies will examine whether passive immunization with a nicotine-specific monoclonal antibody, which decreases nicotine distribution to the brain and prolongs the drug's half-life, is effective in reducing compensation. Characterizing predictors and treatments for compensation may facilitate the use of smoking reduction for the treatment of nicotine addiction, and may also lead to a better understanding of the mechanisms regulating smoking behavior. Relevance to public health: Cigarette smoking is the leading preventable cause of death and disease in the modern world. Although reducing smoking may decrease the harmful effects of cigarettes, the effectiveness of this strategy may be limited by compensatory changes in smoking behavior (for example, increasing the depth of each puff) that occur following smoking reduction. The proposed studies, which will attempt to characterize predisposing factors and a possible treatment for compensation using two animal models of smoking reduction, will provide insights into how to limit this behavior and better understand the potential role of smoking reduction as an approach towards managing tobacco dependence.

描述（由申请人提供）：阐明补偿机制，或因尼古丁供应量减少而发生的吸烟行为变化，对于将减少吸烟特征描述为管理不愿意或无法戒烟的吸烟者的烟草依赖的方法至关重要。我们的实验室开发了两种减少吸烟的啮齿动物模型，在减少每日尼古丁摄入时间或每次输注尼古丁剂量后，观察到尼古丁自我给药的补偿性增加。目前的提案将检查尼古丁戒断的负面情感（即情绪）后果的严重程度（通过颅内自我刺激阈值升高进行评估）是否可以预测剂量或减少的获取模型中的补偿。其他研究将检验使用尼古丁特异性单克隆抗体进行被动免疫是否能有效减少补偿，这种免疫可以减少尼古丁在大脑中的分布并延长药物的半衰期。表征补偿的预测因素和治疗方法可能有助于使用减少吸烟来治疗尼古丁成瘾，也可能导致更好地理解调节吸烟行为的机制。与公共卫生的相关性：吸烟是现代世界导致死亡和疾病的主要可预防原因。尽管减少吸烟可能会减少香烟的有害影响，但该策略的有效性可能会受到减少吸烟后发生的吸烟行为补偿性变化（例如，增加每次吸烟的深度）的限制。拟议的研究将尝试使用两种减少吸烟的动物模型来描述诱发因素和可能的补偿治疗，将为如何限制这种行为提供见解，并更好地了解减少吸烟作为管理烟草依赖的方法的潜在作用。