DRUG ABUSE & NEUROTRANSMITTER RECEPTOR AUTOANTIBODIES

描述（申请人摘要）：最近证明存在 外周液中抗中枢神经系统降解产物的抗体 神经递质受体导致了研究， 这些发现的临床意义。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儿童的影响 免疫系统已经被广泛研究，这些研究通常集中在 经典的免疫参数初步数据显示， 抗肿瘤细胞中μ-δ受体复合物抗原片段的自身抗体 血浆中的阿片类药物滥用者和海洛因自我管理的大鼠。最近 有证据表明，大脑中具有免疫活性的小胶质细胞能够 产生抗原刺激的体液免疫。本申请提出 建立多肽降解自身抗体测定法的实验 μ和δ阿片受体亚单位的产物，并评估 这些自身抗体在μ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，然后在大鼠的血清、CSF和脑区中表达 可卡因、海洛因和可卡因/海洛因静脉自我给药 组合。据推测，滥用阿片受体激动剂 可能导致这些受体产生抗原肽的分解 可以作为外源物质的片段， 免疫系统导致产生针对mu和delta的自身抗体 阿片受体亚单位。自身抗体参与的可能性 神经递质受体在慢性药物滥用是显着的， 可以确定新的机制来确定脆弱性，临床进展， 复发的倾向和通常难以理解的影响 大脑可塑性（定向毒性）的当前概念。

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).