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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目标：甲基苯丙胺(冰毒)的使用量在2009年增加了60%，尽管吸毒者有成瘾、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冰毒成瘾和其他不良后果的影响，我们假设冰毒对青少年和成年人的行为和神经发育基因(轴突引导分子或AGM)的影响是不同的。我们研究了冰毒对青少年和成人大脑中与神经发育、神经发生和神经适应有关的基因表达的影响。方法：对12只青春期雄性小鼠(30天)和12只成年雄性小鼠(10周)灌胃冰毒(5 mg/kg)和生理盐水。连续6天，通过测定3个脑区AGMs的运动能力、刻板反应和mRNA表达。结果：冰毒(5 mg/kg)可增加青春期和成年小鼠的运动活动，但青春期小鼠：(1)高峰作用较晚；(2)运动强度较高；(3)持续时间较长。在两个年龄段的队列中，冰毒治疗后特定AGM在海马体和纹状体的表达水平不同。 结论：冰毒对青春期和成年小鼠的运动和agm基因表达有不同程度的影响。可想而知，冰毒引起的脑内神经发育、形态、行为、认知等一系列改变与海马区、纹状体中特定AGMs基因表达水平的改变有关。与其他策略相结合，这种新的方法可能会澄清冰毒使青少年对毒瘾和其他不良后果的易感性增加的机制。