DEVELOPMENTAL METHAMPHETAMINE INDUCED COGNITIVE DEFICITS

描述：（申请人摘要） 我们发现接触甲基苯丙胺后空间学习障碍 (MA)和MDMA。 基于比较中枢神经系统个体发育， 大鼠的这一时期类似于人的第2 - 3个三月期发育。 啮齿类动物从断奶到青春期的暴露量（相当于儿童期到 青少年发展）的认识不足，尽管事实上， 儿童和青少年有时滥用兴奋剂。 神经化学，我们 发现出生后20天内多巴胺和GFAP的显著变化 和60岁的反应MA，年龄跨越所谓的青少年时期 啮齿动物的发展。 根据这些数据，似乎有 在大脑发育的这些阶段发生的变化 影响MA诱导的神经毒性。 本申请的目的是 研究暴露于MA的认知影响，以确定是否存在 是脆弱的后期。 评估将包括莫里斯 水迷宫空间导航试验，工作试验和顺序试验 条件性位置偏好（CPP）。 影响 海马去甲肾上腺素将根据新的数据进行研究， MDMA可增加断奶前暴露后的NE。 按暴露年龄进行的分窝实验将首先确定 学习和CPP效应的脆弱年龄;这些将随后 这些时期的分窝剂量反应实验显示， 影响，并将调查对工作记忆的影响。 曝光周期 将在出生后第21-30、31-40、41-50和51-60天。 最后一项实验 为了区分先前发现的断奶前脆弱期， 在出生后第11-15或16-20天给药后进行研究。 实验 将开始MA治疗，并根据以下情况继续MDMA治疗 MA实验的结果。 NIDA发现了一个重要的差距， 我们对滥用药物对认知发展影响的理解 和它的神经生物学基质，这个应用程序将开发数据， 填补了MA和MDMA诱导的神经毒性动物模型中的这一空白。"

DESCRIPTION: (Applicant's Abstract) We have found spatial learning deficits after exposure to methamphetamine (MA) and MDMA on postnatal days 11-20. Based on comparative CNS ontogeny, this period in rats is analogous to human 2nd-3rd trimester development. Exposures from weaning to puberty in rodents (equivalent to childhood to adolescent development) are poorly understood, despite the fact that children and adolescents sometimes abuse stimulants. Neurochemically, we have found significant changes in dopamine and GFAP between postnatal day 20 and 60 in response to MA, ages spanning the so-called periadolescent period of rodent development. Based on these data, it appears that there are changes occurring during these stages of brain development which could affect MA-induced neurotoxicity. The purpose of this application is to investigate the cognitive effects of exposure to MA to determine if there are later periods of vulnerability. Assessments will include the Morris water maze test of spatial navigation, tests of working and sequential learning, and conditioned place preference (CPP) behavior. Effects on hippocampal norepinephrine will be investigated based on new data showing that MDMA increases NE after preweaning exposure. Split-litter-by-exposure-age experiments will first determine the most vulnerable ages for learning and CPP effects; these will be followed by split-litter dose-response experiments for those periods showing the largest effects and will investigate effects on working memory. Exposure periods will be postnatal days 21-30, 31-40, 41-50, and 51-60. A final experiment to differentiate the previously found preweaning vulnerable period will be investigated after treatment on postnatal days 11-15 or 16-20. Experiments will begin with MA treatment and proceed to treatment with MDMA depending on the outcome of the MA experiments. NIDA has identified an important gap in our understanding of the effects of drugs of abuse on cognitive development and its neurobiological substrates and this application will develop data to fill this gap in an animal model of MA and MDMA-induced neurotoxicity."