ADOLESCENT AND ADULT MICE RESPOND DIFFERENTLY TO METHAMPHETAMINE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目标：2009年，甲基苯丙胺（METH）的使用量增加了60%，尽管使用者成瘾、神经毒性和认知障碍的风险很高。由于青少年比成年人更容易受到METH成瘾和其他不良后果的影响，我们假设METH对青少年和成年人的行为和神经发育基因（轴突导向分子或AGM）的影响不同。我们研究了METH对青少年和成人大脑中涉及神经发育，神经发生，神经适应的基因表达的影响。方法：我们在12只青春期雄性小鼠（30天）和12只成年雄性小鼠（10周）中比较了METH（5 mg/kg）与生理盐水，每天腹腔注射6天，通过测量3个脑区中AGM的运动活性、刻板性和mRNA表达。研究结果：METH（5 mg/kg）增加青春期和成年小鼠的自发活动，但在青春期小鼠中：（1）峰值效应较晚;（2）运动较高;（3）持续时间较长。在两个年龄组中，海马和纹状体中METH治疗后特异性AGM的表达水平不同。 结论：METH对青春期和成年小鼠的运动和AGM基因表达的影响不同。海马、纹状体中特定AGM mRNA表达水平的改变可能与METH诱导的大脑神经发育、形态、行为、认知变化的级联反应有关。与其他策略相结合，这种新的方法可能会澄清的机制，甲基赋予高度敏感性的青少年成瘾和其他不良后果。

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.