Dopamine Function During Adolescence

描述（由申请人提供）：大多数人第一次接触成瘾性药物是在青春期，在青春期成瘾的发展速度可能比以后的生活要快。本研究验证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的假设。初步数据显示，与年轻成年大鼠（60天）相比，青春期大鼠（28天）的多巴胺摄取基线更高，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终端功能和多巴胺在青春期对行为刺激和药物的反应来验证这一假设。我们将使用快速扫描循环伏安法（FSCV）和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，我们将用FSCV测定28、42、60和90日龄的正常雄性和雌性大鼠在基线和服用可卡因和左旋多巴后多巴胺的摄取和释放动力学。第三，我们将在清醒行为的动物中使用FSCV来确定多巴胺对环境刺激（自愿暴露于新环境）的反应。这些研究应该提供对影响青春期开始吸毒的潜在生物学机制的见解。

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.