ABUSED DRUGS AND DEVELOPMENT OF THE NEUROIMMUNE AXIS

药物滥用与神经免疫轴的发育

• 批准号: 6378278
• 负责人: LISA M SCHROTT
• 金额: $ 10.65万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6378278
• 关键词: adrenocorticotropic hormone; behavior test; behavioral /social science research tag; chick embryo; cocaine; corticosterone; developmental immunology; drug abuse; drug withdrawal; hypothalamic pituitary adrenal axis; immunosuppression; laboratory rat; leukocyte activation /transformation; lipopolysaccharides; metalloendopeptidases; neuroendocrine system; neuroimmunomodulation; neurotransmitter receptor; norepinephrine; opiate alkaloid; psychopharmacology; serotonin; species difference

DESCRIPTION: Applicant's Abstract The developmental consequences of exposure to drugs of abuse and/or withdrawal on interactions between the immune, endocrine, and nervous systems that are essential for the proper execution of the host defense response have not been well studied. This proposal seeks to study these interactions in rats and chicks exposed prenatally to opiates, and opiate or quasi-opiate withdrawal to determine short and long term adverse consequences which could compromise the organism's ability to prevent and survive infection by pathogens. The research is important and timely considering the recent increases in the use of heroin among adolescents, which is likely to increase the number of infants exposed to opiate and opiate withdrawal in utero. In addition, since a common route of heroin administration (and other abused drugs) is intravenous injection, likelihood of exposure to infectious agents, such as HIV, that can be vertically transmitted to the fetus is increased. Thus, it is important to examine how drugs of abuse can affect the development of and interactions between the immune, endocrine, and nervous systems. The proposed studies will examine behaviors influenced by immune system activation (sickness behaviors, autoshaping, and operant responding), endocrine function (hypothalamic-pituitary-adrenal (HPA) axis hormones and their response to acute and chronic stress), and immune function (serum concentrations and tissue gene expression of pro-inflammatory cytokines, macrophage metalloproteinase activity, and antibody response to antigenic challenge) will be examined following opiate exposure and/or withdrawal. Immune system modulation of opiate and quasi-opiate withdrawal will be investigated using both unconditioned and conditioned behavioral measures. Comparisons between true opiate and quasi-opiate withdrawal will permit conclusions as to whether opiate exposure per se is sufficient, in contradistinction to opiate exposure and or withdrawal and associated stresses by itself. Studies will begin to determine causal mechanisms for altered interactions by examining similarities between cocaine exposure and opiate withdrawal and the role of the neurotransmitters serotonin and norepinephrine, since alterations in their activity affect/mediate opiate action, withdrawal phenomena, endocrine, and immune system function. Alterations in HPA axis function will also be examined, as well as immune system activation or suppression concurrent with opiate or withdrawal exposure. This proposal draws on the candidate's past research history studying developmental psychobiology and neural-immune interactions. However, since the candidate has little formal training in pharmacology, appropriate coursework and seminars, along with guidance from an experienced psychopharmacology mentor and consultations/collaborations with researchers in various disciplines will be conducted during the project period. These experiences, coupled with the proposed research project, will help to train and guide the candidate to an independent career studying the developmental consequences of abused drugs, and in particular the complex interactions between the immune, nervous, and endocrine systems.

描述：申请人摘要 接触滥用药物和/或 戒断对免疫、内分泌和神经系统之间相互作用的影响 对正确执行主机防御至关重要的系统 反应没有得到很好的研究。 这项建议旨在研究这些 大鼠和小鸡在产前暴露于阿片类药物，阿片类药物或 准阿片类药物戒断，以确定短期和长期不良反应 可能损害生物体预防能力的后果， 在病原体的感染下存活。 这项研究是重要和及时的 考虑到最近青少年使用海洛因的情况有所增加， 这可能会增加接触阿片类药物的婴儿数量， 子宫内阿片类药物戒断 此外，由于海洛因的常见途径 管理（和其他滥用药物）是静脉注射，可能性 暴露于传染性病原体，如艾滋病毒，可以垂直 传递给胎儿的病毒增加了。 因此，重要的是研究如何 滥用药物会影响发育和相互作用 免疫、内分泌和神经系统。 拟议的研究将审查 受免疫系统激活影响的行为（疾病行为， 自动成形和操作性反应），内分泌功能 （下丘脑-垂体-肾上腺（HPA）轴激素及其对 急性和慢性应激）和免疫功能（血清浓度和 促炎细胞因子的组织基因表达，巨噬细胞 金属蛋白酶活性和抗体对抗原攻击的应答） 将在阿片类药物暴露和/或戒断后进行检查。 免疫系统 阿片和类阿片戒断的调节将使用 无条件和有条件的行为测量。 之间的比较 真正的阿片类药物和准阿片类药物戒断将允许得出以下结论： 与阿片类药物相比，阿片类药物暴露本身是否足够 暴露和/或撤回以及相关的压力本身。 研究将 开始确定因果关系的机制，改变相互作用，通过检查 可卡因接触和阿片剂戒断之间的相似性以及 神经递质血清素和去甲肾上腺素， 它们活性影响/介导阿片作用、戒断现象 内分泌和免疫系统功能。 HPA轴功能改变 还将检查，以及免疫系统激活或抑制 与阿片类药物或戒断暴露同时发生。 该提案借鉴了 候选人过去研究发展心理生物学的历史， 神经免疫相互作用 然而，由于候选人几乎没有正式的 药理学培训，适当的课程和研讨会，沿着 来自经验丰富的精神药理学导师的指导， 与各学科研究人员的协商/合作将是 在项目期间进行。 这些经历，加上 建议的研究项目，将有助于培训和指导候选人， 研究滥用药物的发展后果的独立职业， 尤其是免疫系统、神经系统和 内分泌系统