Dopamine Function 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，成瘾可能在青春期比以后的生活发展得更快。 目前的建议测试的假设，突触前多巴胺机制的成熟事件有助于改变青少年的行为和药理刺激的生物反应性。 其基于初步数据，显示与年轻成年大鼠（60天）相比，青春期大鼠（28天）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。 我们将通过评估多巴胺末梢功能和多巴胺对青春期行为刺激和药物的反应来验证这一假设。 我们将评估多巴胺的摄取和释放，通过青春期的雄性和雌性大鼠使用快速扫描循环伏安法（FSCV）在清醒，行为的动物，并使用体外制剂。 首先，我们将确定突触体和囊泡摄取的贡献，在体内观察到的增强摄取。 其次，我们将确定多巴胺的摄取和释放的动力学在基线和可卡因和L-多巴后，使用FSCV在28，42，60和90天龄的完整的行为的雄性和雌性大鼠。 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。 这些研究应该提供深入了解潜在的生物学机制，影响发病的药物服用在青春期。

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.