Early Exposure to Stimulants as a Risk Factor for Substance Abuse

过早接触兴奋剂是药物滥用的危险因素

• 批准号: 7019211
• 负责人: LINDA J. PORRINO
• 金额: $ 51.96万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7019211
• 关键词: Primates; amphetamines; brain; cocaine; dopamine; human; lead; methylphenidate; model; substance abuse related disorder

DESCRIPTION (provided by applicant): The periods of adolescence and early adulthood are times of risk for the development of addiction and substance abuse disorders. Although there are many risk factors that may increase vulnerability, including family history, genetic background, psychiatric and behavioral disorders, and peer pressure, one important factor is early exposure to drugs during childhood. This has raised concerns about the use of stimulant medications for childhood psychiatric disorders such as attention deficit hyperactivity disorder (ADHD). Most of the studies conducted in children and adults with ADHD have suggested that medication with methylphenidate or amphetamine has either no effect or can be protective from substance abuse disorders. However, it is impossible to distinguish between the effects of the stimulants and ADHD itself. Given that these stimulants can produce dramatic neuroadaptations in the dopamine system and disruptions of dopamine systems may increase vulnerability to drug abuse, the question of long-term adverse consequences of stimulant medication still remains. The overall purpose of this application is to address this question in a non-human primate model. Juvenile rhesus monkeys (approximately 20 mos at the start of the study) will be exposed to oral doses of methylphenidate or amphetamine or placebo for one year. Dopamine function as assessed with positron emission tomography, brain development assessed with magnetic resonance imaging, and markers of physical growth and social development will be measured before treatment commences, at the end of treatment and 3 months after cessation of the medication regimen. Finally, we will assess the reinforcing efficacy of the psychostimulant cocaine once monkeys enter adolescence. These studies are not intended to evaluate all of the potential consequences of stimulant medication in childhood for the treatment of ADHD, but to answer the question of whether stimulant exposure can predispose adolescents to the development of substance abuse disorders.

描述（由申请人提供）：青春期和成年初期是成瘾和药物滥用障碍的风险时代。尽管有许多风险因素可能会增加脆弱性，包括家族史，遗传背景，精神病和行为障碍以及同伴压力，但一个重要因素是童年期间早期接触药物。这引起了人们对使用刺激性药物用于儿童精神疾病（例如注意力缺陷多动障碍（ADHD））的担忧。在患有多动症儿童和成人中进行的大多数研究都表明，用哌醋甲酯或苯丙胺的药物没有作用，或者可以免受药物滥用障碍的保护。但是，不可能区分兴奋剂和多动症本身的影响。鉴于这些兴奋剂可以在多巴胺系统中产生戏剧性的神经适应，并且多巴胺系统的破坏可能会增加对药物滥用的脆弱性，因此仍然存在刺激药物的长期不良后果问题。该应用程序的总体目的是在非人类灵长类动物模型中解决这个问题。一年的幼稚猴猴（在研究开始时约20个MO）将暴露于口服尝试的哌醋甲酯，苯丙胺或安慰剂一年。多巴胺的功能通过正电子发射断层扫描，通过磁共振成像评估的大脑发育以及身体生长和社会发展的标志在治疗开始，治疗结束之前以及停止药物治疗方案后的3个月。最后，一旦猴子进入青春期，我们将评估心理刺激可卡因的增强功效。这些研究并非旨在评估儿童治疗刺激药物的所有潜在后果，而是要回答刺激性暴露是否会使青少年诱发药物滥用障碍的发展的问题。