Dopamine Function During Adolescence

大多数人对成瘾药物的第一次体验发生在青春期和成瘾期间 可能在青春期比以后的生活中发展得更快。目前的建议测试了 突触前多巴胺机制中的成熟事件有助于改变 青少年对行为和药物刺激的生物反应性。这是基于初步的 数据显示更高的基线多巴胺摄取，对可卡因的多巴胺反应增强， 青少年（第28天）与年轻成年（60天）大鼠对可卡因的行为反应。我们将 通过评估多巴胺末梢功能和多巴胺对行为刺激的反应来验证这一假设 和毒品我们将评估男性在青春期的多巴胺摄取和释放， 和雌性大鼠使用快速扫描循环伏安法（FSCV）在清醒的，行为的动物，并在体外使用 准备工作首先，我们将确定突触体和囊泡摄取的贡献，以增强 在体内观察到的摄取。第二，我们将确定基线时多巴胺摄取和释放的动力学 在28、42、60和90日龄行为正常的雄性和雌性动物中， 大鼠第三，我们将确定多巴胺对环境刺激的反应（自愿暴露于 新的环境）中使用FSCV在清醒的行为动物。这些研究应该提供洞察力， potential潜在biological生物mechanisms机制that influence影响the onset发病of drug服用taking服用during青春期during青春期.

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 pharmacologic 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 influencethe onset of drug taking during adolescence.