PHARMACOLOGY AND TOXICOLOGY OF METHAMPHETAMINE ABUSE

描述：(申请人摘要) 这是对格伦·R·汉森博士的高级科学家奖建议。Dr。 汉森是药理学系的终身教授， 犹他大学的毒物学教授。他在吸毒方面一直很活跃。 研究了15年以上，并对 阐明：(A)多巴胺系统在以下引起的神经毒性中的作用 苯丙胺类似物；(B)活性氧物种在调节 苯丙胺类似物引起的单胺能变化；(C) 滥用兴奋剂对神经肽系统的影响；(D)多巴胺的作用 核外和边缘神经调节中的受体亚型 神经肽系统。汉森博士目前将40%-50%的时间用于 研究和学生指导，而他50%-60%的精力被 教学、院系和学院的责任。这位高级科学家 该奖项将允许汉森博士将他的研究努力增加到大约 80%。在获得该奖项的支持期间，他将指导研究 它检验了以下主要假设：(A)产生 多巴胺相关的活性氧物种是导致 术后纹状体单胺能系统出现神经化学缺陷 大剂量甲基苯丙胺(冰毒)；(B)美卡西酮，一种相对较新的 名牌安非他命对人体产生深远的短期和长期影响 锥体外区和边缘单胺能系统 神经毒性潜力；(C)冰毒急性和选择性地改变自然和 多巴胺转运体的可逆功能；(D)低和 高剂量冰毒优先影响间接(纹状体-苍白球) 和直接(纹状体-黑质)至基底节输出的传出通路 (E)神经肽系统的变化发生在人类 暴露在强烈的滥用刺激物中，就像在老鼠身上观察到的那样 在用同样的药物治疗后。研究时间的增加 由高级科学家奖产生的结果将使汉森博士能够 他的实验室需要在新技术方面的专业知识来测试这些 假说，如：(A)自由基分析；(B)转运蛋白功能 和配基分析；(C)神经肽前体的原位杂交 MRNA.这个奖项将帮助汉森博士更有效地指导 本科生、研究生、博士后和 随着这些发展中的科学家成熟和确立，年轻的教职员工水平 一般从事神经科学研究，以及药物滥用研究 很特别。此外，作为一名导师，汉森博士将特别 支持代表人数不足的少数群体参与药物滥用 研究。

DESCRIPTION: (Applicant's Abstract) This is a Senior Scientist Award proposal for Dr. Glen R. Hanson. Dr. Hanson is a tenured professor in the Department of Pharmacology and Toxicology at the University of Utah. He has been active in drug abuse research for over 15 years and has made important contributions to elucidating: (a) the role of dopamine systems in neurotoxicity caused by amphetamine analogs; (b) the role of reactive oxygen species in mediating monoaminergic changes caused by amphetamine analogs; (c) the influence of the stimulants of abuse on neuropeptide systems; (d) the role of dopamine receptor subtypes in the regulation of extrapyrarnidal and limbic neuropeptide systems. Dr. Hanson currently devotes 40-50% of his time to research and student mentoring while 50-60% of his effort is occupied by teaching, departmental and college responsibilities. This Senior Scientist Award will allow Dr. Hanson to increase his research effort to approximately 80%. During the time of support by this award, he will direct research which tests the following principal hypotheses: (a) the generation of dopamine-related reactive oxygen species is a major contributor to the neurochemical deficits occurring in the striatal monoaminergic systems after high doses of methamphetamine (METH); (b) methcathinone, a relatively new designer amphetamine, exerts profound short-and long-term effects on extrapyramidal and limbic monoaminergic systems and has significant neurotoxic potential; (c) METH acutely and selectively alters the nature and function of the dopamine transporter in a reversible manner; (d) low and high doses of METH preferentially influence the indirect (striatal-pallidal) and direct (striatal-nigral) efferent pathways to the basal ganglia output nuclei, respectively; (e) changes in neuropeptide systems occur in humans exposed to the potent stimulants of abuse much like that observed in rats after treatment with these same drugs. The increase in research time resulting from a Senior Scientist Award will allow Dr. Hanson to develop expertise in technologies new to his laboratory required to test these hypotheses, such as: (a) free radical analysis; (b) transporter function and ligand assays; (c) in situ hybridization for neuropeptide precursor mRNA. This award will help Dr. Hanson to mentor more effectively inexperienced researchers at the undergraduate, graduate, postdoctoral and young faculty levels as these developing scientists mature and establish themselves in neuroscience research in general, and drug abuse research in particular. In addition, as a mentor Dr. Hanson will be especially supportive of the involvement of underrepresented minorities in drug abuse research.