ABUSED DRUGS AND DEVELOPMENT OF THE NEUROIMMUNE AXIS

药物滥用与神经免疫轴的发育

• 批准号: 2897649
• 负责人: LISA M SCHROTT
• 金额: $ 9.69万
• 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/2897649
• 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：申请者摘要 接触滥用和/或药物的发育后果 戒断免疫、内分泌和神经之间的相互作用 对主机防御的正确执行至关重要的系统 反应还没有得到很好的研究。本提案旨在研究这些问题 大鼠和雏鸡产前暴露于阿片类药物，以及阿片类药物或 确定短期和长期不良反应的准阿片类药物戒断 可能会损害生物体预防和 在病原体的感染下存活下来。这项研究是重要的和及时的。 考虑到最近青少年中海洛因使用量的增加， 这可能会增加接触鸦片类药物的婴儿数量， 阿片类药物在宫内戒断。此外，由于海洛因的一条常见路线 给药(和其他滥用药物)是静脉注射，可能 暴露于感染性因素，如艾滋病毒，可能是垂直的 传给胎儿的是增加的。因此，重要的是研究如何 滥用药物会影响儿童精神疾病的发展和相互作用 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、 自动整形和操作员响应)、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 促炎症细胞因子、巨噬细胞的组织基因表达 金属蛋白酶活性和对抗原攻击的抗体反应) 将在阿片类药物暴露和/或戒断后进行检查。免疫系统 阿片剂和准阿片剂戒断的调节将使用 无论是无条件的还是有条件的行为措施。比较以下几种情况 真正的阿片剂和准阿片剂戒断将允许得出以下结论 与鸦片类药物相比，鸦片类药物本身的暴露是否足够 暴露和/或退缩和相关的压力本身。研究将会 通过检查开始确定改变交互作用的原因机制 可卡因暴露与阿片类药物戒断的相似性及其作用 神经递质5-羟色胺和去甲肾上腺素 它们的活性影响/调节阿片类药物的作用，戒断现象， 内分泌和免疫系统功能。HPA轴功能的改变 也将检查免疫系统的激活或抑制 同时接触鸦片类药物或戒断药物。这项建议借鉴了 候选人过去的研究历史，学习发展心理生物学和 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，以及 由经验丰富的精神药理学导师和 将与不同学科的研究人员进行磋商/合作 在项目期间进行。这些经历，再加上 拟议的研究项目，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、神经和免疫之间的复杂相互作用 内分泌系统。