DRUG ABUSE & NEUROTRANSMITTER RECEPTOR AUTOANTIBODIES

吸毒

• 批准号: 6042620
• 负责人: JAMES E SMITH
• 金额: $ 7.25万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6042620
• 关键词: antibody formation; autoantibody; brain mapping; cerebrospinal fluid; cocaine; drug abuse; drug addiction; enzyme linked immunosorbent assay; heroin; humoral immunity; laboratory rat; microdialysis; neurotransmitter receptor; opioid receptor; peptides; protein degradation; protein sequence; protein structure; technology /technique development; tissue /cell culture; western blottings

DESCRIPTION (applicant's abstract): Recent demonstrations of the presence of antibodies in peripheral fluids to degradation products of central neurotransmitter receptors has led to studies to identify the potential clinical relevance of these findings. Elevated levels of autoantibodies to neurotransmitter receptors have been found in the serum of individuals suffering from epilepsy and ischemic stroke. The effects of drug abuse on the immune system has been widely studied, with these studies generally focused on classic immune parameters. Preliminary data have shown elevated levels of autoantibodies to antigenic fragments of the mu-delta receptor complex in the plasma of human opiate abusers and in heroin self-administering rats. Recent evidence indicate that immunocompetent microglia in the brain are capable of developing an antigen stimulated humoral immunity. This application proposes experiments to establish assays for autoantibodies for polypeptide degradation products of the mu and delta opioid receptor subunits and to assess the presence of these autoantibodies in mu receptor (expressing transfected CHO and C6 glioma cells) and delta receptor (NG 108 15 neuroblastoma x glioma) expressing cell lines and then in sera, CSF and brain regions of rats intravenously self-administering cocaine, heroin and cocaine/heroin combinations. It is hypothesized that abuse of agonists for opiate receptors may result in the breakdown of these receptors producing antigenic peptide fragments that can serve as exogenic substances which are recognized by the immune system resulting in the production of autoantibodies to the mu and delta opioid receptor subunits. The potential for the involvement of autoantibodies to neurotransmitter receptors in the chronic abuse of drugs is significant and could identify new mechanisms for determining vulnerability, clinical progress, the propensity for relapse and effects that are often difficult to understand with current concepts of brain plasticity (directed toxicities).

描述（申请人的摘要）：最近的存在证明 外周液中针对中枢神经系统降解产物的抗体 神经递质受体引发了研究以确定潜在的 这些发现的临床相关性。自身抗体水平升高 在个体的血清中发现了神经递质受体 患有癫痫和缺血性中风。药物滥用对身体的影响 免疫系统已被广泛研究，这些研究通常集中于 经典的免疫参数。初步数据显示， mu-delta 受体复合物抗原片段的自身抗体 人类鸦片滥用者和海洛因自我给药大鼠的血浆。最近的 有证据表明，大脑中具有免疫功能的小胶质细胞能够 产生抗原刺激体液免疫。本申请提出 建立多肽降解自身抗体测定方法的实验 mu 和 delta 阿片受体亚基的产物并评估 mu 受体（表达转染的 CHO 和 C6 神经胶质瘤细胞）和 δ 受体（NG 108 15 神经母细胞瘤 x 神经胶质瘤） 表达细胞系，然后进入大鼠血清、脑脊液和大脑区域 静脉自我注射可卡因、海洛因和可卡因/海洛因 组合。据推测，阿片受体激动剂的滥用 可能会导致这些受体分解，产生抗原肽 可以作为被识别的外源物质的片段 免疫系统产生针对 mu 和 delta 的自身抗体 阿片受体亚基。自身抗体参与的可能性 长期滥用药物对神经递质受体的影响是显着的 可以确定确定脆弱性、临床进展的新机制， 复发的倾向和通常难以理解的影响 与当前的大脑可塑性概念（定向毒性）。