Dopamine Function During Adolescence

青春期的多巴胺功能

• 批准号: 6876278
• 负责人: Cynthia M Kuhn
• 金额: $ 26.41万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-25 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6876278
• 关键词: age difference; behavior test; chordate locomotion; cocaine; dopamine; dopamine transporter; gender difference; juvenile animal; laboratory rat; levodopa; neuropharmacology; neuropsychology; neurotransmitter transport; nucleus accumbens; protein structure function; synaptosomes; wakefulness

DESCRIPTION (provided by applicant): The first experience most people have with addictive drugs occurs during adolescence and addiction may develop more quickly during adolescence than later in life. The present proposal tests the hypothesis that maturational events in presynaptic dopamine mechanisms contribute to the altered biologic reactivity of adolescents to behavioral and pharmacological stimuli. It is based on preliminary data showing greater baseline dopamine uptake, enhanced dopamine responses to cocaine and enhanced behavioral responses to cocaine in adolescent (day 28) compared to young adult (60 day old) rats. We will test this hypothesis by evaluating dopamine terminal function and dopamine responses to behavioral stimuli and drugs through adolescence. We will evaluate dopamine uptake and release through adolescence in male and female rats using both fast scan cyclic voltammetry (FSCV) in awake, behaving animals, and using in vitro preparations. First, we will determine the contribution of synaptosomal and vesicular uptake to the enhanced uptake observed in vivo. Second, we will determine the kinetics of dopamine uptake and release at baseline and after cocaine and L-Dopa using FSCV in 28, 42, 60 and 90 day old intact behaving male and female rats. Third, we will determine dopamine responses to an environmental stimulus (voluntary exposure to a novel environment) using FSCV in awake behaving animals. These studies should provide insight into potential biologic mechanisms that influence the onset of drug taking during adolescence.

描述（由申请人提供）：大多数人对成瘾药物的第一次体验发生在青春期，并且成瘾在青春期可能比晚年发展得更快。 本提案测试了这样的假设：突触前多巴胺机制中的成熟事件导致青少年对行为和药理刺激的生物反应性改变。 它基于初步数据，显示与年轻成年（60 天龄）大鼠相比，青少年（第 28 天）大鼠的基线多巴胺摄取量更大，对可卡因的多巴胺反应增强，对可卡因的行为反应增强。 我们将通过评估青春期的多巴胺末端功能以及多巴胺对行为刺激和药物的反应来检验这一假设。 我们将使用快速扫描循环伏安法（FSCV）在清醒、行为动物中以及使用体外制剂来评估雄性和雌性大鼠在青春期的多巴胺摄取和释放。 首先，我们将确定突触体和囊泡摄取对体内观察到的增强摄取的贡献。 其次，我们将使用 FSCV 在 28、42、60 和 90 天龄的完整行为雄性和雌性大鼠中确定基线以及可卡因和左旋多巴后多巴胺摄取和释放的动力学。 第三，我们将使用清醒行为动物的 FSCV 确定多巴胺对环境刺激（自愿暴露于新环境）的反应。 这些研究应该可以深入了解影响青春期吸毒开始的潜在生物学机制。