INDIVIDUAL DIFFERENCES IN RESPONSE TO AMPHETAMINE

最近的理论将药物滥用描述为一种障碍，不仅涉及正向激励动机，还包括一种 障碍的特征也是失去抑制性控制。在这个项目中，我们将使用一只实验动物 确定风险相关特征之间关联的关键神经机制的模型 以及药物滥用，这些问题不能完全利用人类受试者来解决。我们的工作假设是 风险相关特征中的个体差异，如寻求回报和抑制，在药物滥用中起着作用 脆弱性和这两种行为结构中的个体差异是由可分离的 神经系统。而奖赏寻求和抑制无疑涉及复杂和重叠的神经 环路，我们目前的知识表明，奖赏寻求被上升的中皮质边缘所取代 多巴胺(DA)系统，而抑制由涉及DA和DA的额叶皮质区域提供。 5-羟色胺(5-HT)。解剖学研究也表明，内侧前额叶皮质(MPFC)是 与奖赏寻求和抑制有关，而眼眶前额叶皮质(OFC)与 抑制力。将对这些神经系统进行检查，以确定它们在奖赏关联中的作用。 用毒品奖赏寻求和抑制。将评估大鼠在寻求奖励时的个体差异 和抑制使用各种行为测试，然后将评估苯丙胺奖励，DA和5- 用体内伏安法和电生理学评价羟色胺转运体功能和神经活动 学习。我们预测，高奖赏寻求和低抑制的老鼠将最容易受到 安非他明和相关药物的回报作用。此外，我们预测奖励高的老鼠 寻求和低抑制将对与药物竞争的非药物替代增强剂最敏感 奖励，这可能对设计有效的药物滥用预防具有重要的翻译意义 对人类的干预策略。最后，我们预测个体在寻求奖赏和寻求奖赏上的差异 抑制将与伏隔核mPFC内DA和5-HT系统的差异有关 和/或OFC。这些结果，结合人类行为药理学和神经成像结果 项目2，将提供更全面的了解涉及风险相关特征的神经系统 与量身定做的禁毒预防干预信息的设计相关。

Recent theories describe drug abuse as a disorder involving not only positive incentive motivation, but as a disorder also charactered by a loss of inhibitory control. In this project, we will use a laboratory animal model to determine the critical neural mechanisms that underlie the association between risk-related traits and drug abuse, questions that cannot be addressed fully using human subjects. Our working hypothesis is that individual differences in the risk-related traits, reward seeking and inhibition, play a role in drug abuse vulnerability and that individual differences in these two behavioral constructs are mediated by dissociable neural systems. While reward seeking and inhibition undoubtedly involve complex and overlapping neural circuits, our current knowledge suggests that reward seeking is subserved by ascending mesocorticolimbic dopamine (DA) systems, whereas inhibition is subserved by frontal cortical regions involving both DA and serotonin (5-HT). Anatomical studies have also revealed that the medial prefrontal cortex (mPFC) is implicated in both reward seeking and inhibition, whereas the orbitofrontal cortex (OFC) is implicated in inhibition. These neural systems will be examined to determine their role in the association of reward seeking and inhibition with drug reward. Rats will be assessedfor individual differences in reward seeking and inhibition using a variety of behavioral tests and then will assessed for amphetamine reward, DA and 5- HT transporter function, and neural activity assessed by in vivo voltammetry and electrophysiological studies. We predict that rats that are high in reward seeking and low in inhibition will be most vulnerable to the rewarding effect of amphetamine and related drugs. Also, we predict that rats that are high in reward seeking and low in inhibition will be most sensitive to nondrug alternative reinforcers that compete with drug reward, which may have important translational implications for the design of effective drug abuse prevention intervention strategies in humans. Finally, we predict that individual differences in reward seeking and inhibition will be associatedwith differences in DA and 5-HT systems within the nucleus accumbens, mPFC and/or OFC. These results, combined with the human behavioral pharmacology and neuroimaging results in Project 2, will provide a more comprehensive understanding the neural systems involved in risk-related traits relevant to the design of tailored anti-drug prevention intervention messages.