Effects of Passive Immunization on Nicotine Dependence in Rats

被动免疫对大鼠尼古丁依赖的影响

• 批准号: 7426328
• 负责人: Samuel A. Roiko
• 金额: $ 2.54万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-14 至 2009-01-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7426328
• 关键词: Abstinence; Abstinence Syndrome; Action Potentials; Acute; Address; Adverse effects; Affinity; Antibodies; Antibody Affinity; Attenuated; Behavior; Behavioral; Binding; Brain; Cessation of life; Characteristics; Chronic; Clinical; Data; Dose; Drug Addiction; Drug Delivery Systems; Drug Kinetics; Ensure; Goals; Health; Immunization; Immunoglobulin G; Immunotherapy; Individual; Intravenous; Maintenance; Modeling; Monoclonal Antibodies; Nicotine; Nicotine Dependence; Nicotine Withdrawal; Nicotinic Antagonists; Passive Immunization; Passive Transfer of Immunity; Population; Precipitation; Protocols documentation; Range; Rattus; Rewards; Self Administration; Serum; Smoke; Smoker; Smoking; Time; Tobacco smoke; United States; Vaccination; Vaccines; Withdrawal; Withholding Treatment; addiction; clinical effect; clinically relevant; desire; erythroidine; insight; novel strategies; passive antibodies; research study; smoking cessation

DESCRIPTION (provided by applicant): Smoking is the leading cause of preventable deaths worldwide, and new therapies are needed to help smokers quit. Nicotine is the primary addictive component of tobacco smoke, therefore blocking the actions of nicotine is a logical strategy for developing smoking cessation treatments. Immunization is a novel approach to attenuate the effects of nicotine by targeting the drug rather than the brain. Vaccination against nicotine alters nicotine pharmacokinetics and nicotine self-administration, yet the efficacy of vaccination may be limited by variable serum antibody levels, a delay in achieving effective antibody titers, and a lack of control over antibody affinity. Passive immunization with a monoclonal antibody against nicotine may provide advantages over vaccination in treating nicotine dependence by allowing manipulation of antibody serum levels and antibody affinity. This proposal will examine the effects of a monoclonal antibody against nicotine on nicotine distribution to the brain in rats, nicotine self-administration, and its ability to precipitate nicotine withdrawal over a range of doses. These studies will clarify the mechanisms of action by which immunization attenuates nicotine's effects and the clinical utility of passive immunization. In the United States, 20-25% of the population are smokers, and the many severe health consequences due to smoking are widely known. Nicotine is the main addictive component of tobacco smoke. This proposal will examine the use of immunotherapy such as vaccination to block the effects of nicotine, and develop more treatments to help individuals stop smoking.

描述（由申请人提供）：吸烟是全球可预防死亡的主要原因，需要新的疗法来帮助吸烟者戒烟。尼古丁是烟草烟雾的主要成瘾成分，因此阻止尼古丁的作用是开发戒烟治疗的逻辑策略。免疫是一种新颖的方法，可以通过靶向药物而不是大脑来减轻尼古丁的影响。针对尼古丁的疫苗接种会改变尼古丁药代动力学和尼古丁自我给药，但是疫苗接种的功效可能受到可变血清抗体水平，实现有效抗体滴度的延迟以及缺乏对抗体亲和力的控制的延迟。用抗尼古丁的单克隆抗体被动免疫可以通过操纵抗体血清水平和抗体亲和力来治疗尼古丁依赖性方面具有优势。该提案将检查单克隆抗体对尼古丁对大鼠尼古丁分布的影响，尼古丁自我给药及其在一系列剂量上沉淀尼古丁戒断的能力。这些研究将阐明免疫能够减轻尼古丁的作用和被动免疫的临床实用性的作用机制。在美国，有20-25％的人口是吸烟者，由于吸烟而引起的许多严重健康后果是广为人知的。尼古丁是烟草烟雾的主要成瘾成分。该建议将检查使用免疫疗法的使用，例如疫苗接种以阻止尼古丁的作用，并开发更多的治疗方法来帮助个体戒烟。