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 岁儿童被诊断患有注意力缺陷/多动障碍 (ADHD)，并且有 400 万儿童长期接受药物治疗来治疗 ADHD。哌醋甲酯 (MPD) 和安非他明 (Amph) 可控制大多数接受治疗的患者的 ADHD。然而，人们担心接受 MPD 或 Amph 治疗的儿童在行为、神经化学、生长速度和药物滥用方面的长期发育变化。拟议的研究将检验以下假设：慢性 MPD 或 Amph 会导致青春期前恒河猴的长期行为、生理和神经化学改变。口服自行给药技术将在治疗儿童 ADHD 的治疗窗内提供 MPD 或 Amph 的无压力给药。具体目标 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、食物摄入量和身体生长速度。 MPD 或 Amph 给药 18 个月后，还将进行安非他明行为敏感性测试。具体目标 2 将检验以下假设：慢性 MPD 或 Amph 会改变青春期前猴子发育中的中枢神经系统，包括小胶质细胞的慢性激活和多巴胺能功能的长期改变。多巴胺能功能的测量包括多巴胺转运蛋白、多巴胺 D2 受体和安非他明刺激的多巴胺释放的水平。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。具体目标 4 将检验以下假设：之前接触过 MPD 或 Amph 的猴子具有较高的自我服用可卡因倾向。拟议的研究对治疗剂量的 MPD 和 Amph 对青春期前非人灵长类动物的慢性影响进行了全面的跨学科评估。这些研究将增进对长期低剂量兴奋剂治疗的长期神经化学、行为和生理影响的理解，并可直接转化应用于多动症儿童的药物治疗。