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）：大多数人在青春期和成瘾期间发生的第一个成瘾性药物在青春期可能比以后的生活更快地发展。 本提案检验了以下假设：突触前多巴胺机制中的成熟事件有助于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，与年轻人（60天大的）大鼠相比，青少年（第28天）对可卡因的多巴胺吸收，增强了对可卡因的多巴胺反应以及对可卡因的行为反应增强。 我们将通过评估多巴胺终末功能和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，行为动物和使用体外制剂中使用快速扫描循环伏安法（FSCV）评估多巴胺的摄取并通过青春期释放。 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，我们将在28、42、42、60和90天龄的雄性和雌性大鼠中使用FSCV确定多巴胺摄取的动力学和在基线和L-DOPA之后的动力学。 第三，我们将使用FSCV在清醒的动物中确定多巴胺对环境刺激的反应（自愿接触新的环境）。 这些研究应洞悉影响青春期药物服用开始的潜在生物学机制。