DEVELOPMENTAL METHAMPHETAMINE INDUCED COGNITIVE DEFICITS

描述：(申请人摘要) 我们发现在接触甲基苯丙胺后存在空间学习障碍 (MA)和MDMA在出生后11-20天。基于比较中枢神经系统个体发育学， 大鼠的这一时期类似于人类第二至第三个三个月的发育。 啮齿动物从断奶到青春期的暴露(相当于童年到青春期 (青春期发育)，尽管事实是 儿童和青少年有时会滥用兴奋剂。在神经化学方面，我们 在出生后第20天发现多巴胺和胶质纤维酸性蛋白有显著变化 60岁是对MA的反应，这些年龄跨越了所谓的青春期 啮齿动物的发育。根据这些数据，似乎有 在大脑发育的这些阶段发生的变化可能 影响MA诱导的神经毒性。此应用程序的目的是 调查接触MA对认知的影响，以确定是否存在 是后期的脆弱时期。评估将包括莫里斯夫妇 空间导航水迷宫试验、工作试验和时序试验 学习和条件性位置偏好(CPP)行为。对……的影响 根据新的数据显示，将对海马区去甲肾上腺素进行研究 在断奶前暴露后，MDMA增加了NE。 按暴露年龄分割垃圾的实验将首先决定大多数 脆弱的学习年龄和CPP影响；紧随其后的是 裂落物剂量-反应实验显示最大的时期 影响，并将调查对工作记忆的影响。暴露期 将是出生后21-30天、31-40天、41-50天和51-60天。最后一次实验 为了区分先前发现的断奶前易损期， 在出生后第11-15天或16-20天进行治疗后的调查。实验 将从MA治疗开始，然后根据以下情况继续使用MDMA治疗 MA实验的结果。Nida已经发现了一个重要的缺口 我们对滥用药物对认知发展影响的理解 和它的神经生物底物，这项应用将开发数据以 在MA和MDMA诱导的神经毒性的动物模型中填补这一空白。

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."