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

基本信息

批准号：
7369723
负责人：
LINDA J. PORRINO
金额：
$ 57.43万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
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/7369723
关键词：
13 year old 15 year old 17 year old 20 year old Academic achievement Address Adolescence Adolescent Adult Age-Months Amphetamines Animal Model Animals Attention deficit hyperactivity disorder Behavior Behavior Disorders Brain Child Childhood Chronic Classification Clinical Cocaine Cognitive Complex Corpus striatum structure Data Development Diagnosis Disease Disruption Dopamine Dopamine D2 Receptor Dopamine Receptor Dopaminergic Agents Dose Drug Exposure Drug abuse Drug usage Evaluation Exposure to Family history of Fibrinogen Genetic Growth Health Human Illicit Drugs Intervention Long-Term Effects Longevity Macaca mulatta Magnetic Resonance Imaging Maternal Exposure Measures Mental disorders Methylphenidate Modeling Monkeys Neuroanatomy Oral Peer Pressure Pharmaceutical Preparations Placebos Population Positron-Emission Tomography Predisposing Factor Pregnancy Psychological reinforcement Psychopathology Purpose Reporting Research Research Personnel Risk Risk Factors Severities Social Development Staging Substance abuse problem Surveys Time Treatment Protocols United States Substance Abuse and Mental Health Services Administration Withholding Treatment addiction brain morphology dopamine system dopamine transporter morphometry neuroadaptation neurochemistry nonhuman primate prescription document prescription procedure programs psychostimulant social tomography

项目摘要

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 protectivefrom 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 overallpurpose 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 positronemission 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 oftreatment 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.

青春期和成年早期是成瘾和成瘾发展风险的时期药物滥用障碍。尽管有许多风险因素可能会增加脆弱性，但包括家族史，遗传背景，精神病和行为障碍以及同伴压力，一个重要的因素是童年期间早期接触药物。这引起了人们对使用刺激药物来用于儿童精神疾病，例如注意力缺陷多动症疾病（多动症）。在患有多动症的儿童和成人中进行的大多数研究表明用哌醋甲酯或苯丙胺的药物没有作用，也可以是保护药物滥用障碍。但是，不可能区分兴奋剂和多动症本身。鉴于这些兴奋剂可以在多巴胺系统和多巴胺系统的破坏可能会增加对滥用毒品的脆弱性，刺激药物的长期不利后果的问题仍然存在。总体用途此应用程序是在非人类灵长类动物模型中解决这个问题。少年恒河猴（研究开始时约20个MO）将暴露于口服哌醋甲酯或苯丙胺或安慰剂一年。多巴胺的功能如额度排放评估层析成像，通过磁共振成像评估的大脑发育和物理标记在治疗结束之前，将在治疗开始之前衡量成长和社会发展停止药物治疗方案后3个月。最后，我们将评估增强功效曾经猴子进入青春期的心理刺激可卡因。这些研究无意评估儿童时期刺激药物的所有潜在后果多动症，但要回答刺激性暴露是否可以使青少年倾向于滥用药物障碍的发展。