ADOLESCENT AND ADULT MICE RESPOND DIFFERENTLY TO METHAMPHETAMINE

青少年和成年小鼠对甲基苯丙胺的反应不同

• 批准号: 8357963
• 负责人: Bertha K Madras
• 金额: $ 1.38万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357963
• 关键词: Adolescent; Adult; Affect; Age; Behavior; Behavioral; Brain; Brain region; Corpus striatum structure; Funding; Gene Expression; Genes; Grant; Hippocampus (Brain); Impaired cognition; Locomotion; Male Adolescents; Measures; Methamphetamine; Methamphetamine dependence; Motor Activity; Mus; National Center for Research Resources; New England; Predisposition; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Saline; Source; United States National Institutes of Health; addiction; adverse outcome; axonal guidance; base; cognitive change; cohort; cost; high risk; mRNA Expression; male; neuroadaptation; neurodevelopment; neurogenesis; neurotoxicity; novel strategies; stereotypy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. AIMS: Methamphetamine (METH) use increased 60 percent in 2009, even though users are at high risk for addiction, neurotoxicity and cognitive impairment. As adolescents are more susceptible to METH addiction and other these adverse consequences than adults, we hypothesized that METH affects behaviors and neurodevelopmental genes (axonal guidance molecules or AGMs) differently in adolescent and adults. We investigated the effects of METH on expression of genes implicated in neurodevelopment, neurogenesis, neuroadaptation in adolescent and adult brain. METHODS: We compared METH (5 mg/kg) with saline in 12 adolescent male (30 days) and 12 adult male mice (10 weeks), given i.p. daily for 6 days, by measuring locomotor activity, stereotypy and mRNA expression of AGMs in 3 brain regions. RESULTS: METH (5 mg/kg) increased locomotor activity in adolescent and adult mice, but in the adolescent mice: (1) peak effects were later; (2) locomotion was higher; (3) duration was longer. In the two age cohorts, expression levels of specific AGMs differed following METH treatment in hippocampus and striatum. CONCLUSIONS: METH affected locomotion and AGM gene expression differently in adolescent and adult mice. Altered mRNA expression levels of specific AGMs in hippocampus, striatum conceivably are associated with the cascade of METH-induced neurodevelopmental, morphological, behavioral, cognitive changes in brain. Combined with other strategies, this novel approach may clarify the mechanisms by which METH confers heightened susceptibility of the adolescent to addiction and to other adverse consequences.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 目的：甲基苯丙胺（甲基苯丙胺）的使用在2009年增加了60％，即使用户处于成瘾，神经毒性和认知障碍的高风险。由于青少年比成年人更容易受到MET成瘾和其他不良后果的影响，因此我们假设Meth会影响青少年和成年人的行为和神经发育基因（轴突引导分子或AGMS）。我们研究了METH对与神经发育，神经发生，神经适应青春期和成人大脑的基因表达的影响。方法：我们将甲基（5 mg/kg）与盐水中的盐水（30天）和12名成年男性小鼠（10周）进行了比较。每天持续6天，通过测量3个大脑区域中AGM的运动活性，定型观念和mRNA表达。结果：甲基（5 mg/kg）在青少年和成年小鼠中增加了运动活性，但在青春期小鼠中：（1）峰值效应较晚； （2）运动更高； （3）持续时间更长。在两个年龄的队列中，海马和纹状体中的甲基苯丙胺处理后，特异性AGM的表达水平有所不同。 结论：在青少年和成年小鼠中，甲基苯丙胺受影响的运动和AGM基因表达不同。纹状体改变了海马中特异性AGM的mRNA表达水平，可以想象与甲基甲基级别的神经发育，形态学，行为，行为，认知变化有关。结合其他策略，这种新颖的方法可以阐明甲基对青少年对成瘾和其他不利后果的敏感性增强的机制。