Oral Self-Dosing/Behavioral Assessment

口服自我给药/行为评估

• 批准号: 7105110
• 负责人: MICHAEL R WEED
• 金额: $ 73.76万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7105110
• 关键词: Macaca mulatta; amphetamines; attention deficit disorder; behavior test; behavioral /social science research tag; behavioral habituation /sensitization; behavioral medicine; body weight; central nervous system; circadian rhythms; cocaine; developmental neurobiology; dopamine receptor; dopamine transporter; executive function; growth /development; human therapy evaluation; mental disorder chemotherapy; methylphenidate; microglia; middle childhood (6-11); neurochemistry; nutrient intake activity; oral administration; therapy adverse effect

DESCRIPTION (provided by applicant): Approximately 3-5% of children ages 3-17 in the U.S. are diagnosed with Attention Deficit / Hyperactivity Disorder (ADHD), and 4 million children are medicated chronically to treat ADHD. Methylphenidate (MPD) and amphetamine (Amph), control ADHD in the majority of those treated. However, there are concerns over long-lasting developmental changes in behavior, neurochemistry, growth rates and potential for substance abuse in children treated with MPD or Amph. The proposed research will test the hypothesis that chronic MPD or Amph results in long-term behavioral, physiologic and neurochemical alterations in preadolescent rhesus monkeys. Oral self-dosing techniques will provide non-stressful administration of MPD or Amph in doses within the therapeutic window for treatment of ADHD in children. Specific Aim 1 will determine if chronic MPD or Amph alters physiological development of preadolescent monkeys including circadian rhythms, body weights, food intake, and body growth rate. After 18 months of MPD or Amph administration, tests for behavioral sensitization to amphetamine will also be performed. Specific Aim 2 will test the hypothesis that chronic MPD or Amph alters the developing central nervous system including chronic activation of microglia and long-lasting alterations in dopaminergic function in preadolescent monkeys. Measures of dopaminergic function will include levels of dopamine transporters, dopamine D2 receptors and amphetamine-stimulated dopamine release. Specific Aim 3 will determine the effects of chronic MPD or Amph on development of executive function including inhibitory control and attentional set-shifting. Specific Aim 4 will test the hypothesis that monkeys previously exposed to MPD or Amph have a higher propensity to self-administer cocaine. The proposed studies provide a comprehensive interdisciplinary evaluation of the chronic effects of therapeutic doses of MPD and Amph in preadolescent nonhuman primates. These studies will advance understanding of the long-term neurochemical, behavioral and physiologic effects of chronic low-dose stimulant treatments and have direct translational application to the medication of children with ADHD.

描述（由申请人提供）：在美国，大约3-5%的3-17岁儿童被诊断为注意力缺陷/多动障碍（ADHD）， 400万儿童长期服用药物治疗ADHD。哌醋甲酯（MPD）和安非他明（Amph）在大多数接受治疗的患者中都能控制多动症。然而，人们对MPD或Amph治疗儿童在行为、神经化学、生长速度和药物滥用方面的长期发育变化感到担忧。拟议的研究将测试慢性MPD或Amph导致青春期前恒河猴长期行为，生理和神经化学改变的假设。口服自我给药技术将在治疗窗口内提供无压力的MPD或Amph给药，用于治疗儿童多动症。特异性目标1将确定慢性MPD或Amph是否会改变青春期前猴子的生理发育，包括昼夜节律、体重、食物摄入和身体生长速度。在服用MPD或安非他明18个月后，还将进行对安非他明行为敏感性的测试。特异性目标2将测试慢性MPD或Amph改变发育中的中枢神经系统的假设，包括小胶质细胞的慢性激活和青春期前猴子多巴胺能功能的长期改变。多巴胺能功能的测量将包括多巴胺转运体、多巴胺D2受体和安非他明刺激的多巴胺释放水平。具体目标3将确定慢性MPD或Amph对执行功能发展的影响，包括抑制控制和注意力转移。Specific Aim 4将测试先前暴露于MPD或Amph的猴子更倾向于自我服用可卡因的假设。拟议的研究提供了一个全面的跨学科评估治疗剂量的MPD和Amph在青春期前非人灵长类动物的慢性效应。这些研究将促进对慢性低剂量兴奋剂治疗的长期神经化学、行为和生理效应的理解，并对多动症儿童的治疗有直接的转化应用。