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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 目的：2009 年，甲基苯丙胺 (METH) 的使用量增加了 60%，尽管使用者面临成瘾、神经毒性和认知障碍的高风险。由于青少年比成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人的行为和神经发育基因（轴突引导分子或 AGM）的影响不同。我们研究了冰毒对青少年和成人大脑神经发育、神经发生、神经适应相关基因表达的影响。方法：我们对 12 只青春期雄性小鼠（30 天）和 12 只成年雄性小鼠（10 周）进行腹腔注射，比较了冰毒（5 mg/kg）和生理盐水。每天持续 6 天，通过测量 3 个大脑区域的运动活动、刻板性和 AGM 的 mRNA 表达。结果：冰毒（5 mg/kg）增加了青春期和成年小鼠的运动活动，但在青春期小鼠中：（1）峰值作用较晚； (2)运动能力较高； (3)持续时间较长。在两个年龄组中，METH 治疗后海马和纹状体中特定 AGM 的表达水平有所不同。 结论：冰毒对青少年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、认知变化的级联有关。与其他策略相结合，这种新颖的方法可能会阐明冰毒使青少年对成瘾和其他不良后果更加敏感的机制。