Project 4

摘要 摇头丸(摇头丸)和氯胺酮是滥用毒品，越来越受欢迎。与更多 然而，人们对传统兴奋剂或麻醉剂的作用方式、主观影响、 以及这些效应如何促进继续使用。我们的目标是开发一种理论上知情的 亚甲基四氢叶酸甲酯、甲基苯丙胺和氯胺酮对小鼠神经行为的影响 处理风险和回报的电路，这些电路的连接性，以及这些电路和它们的 连通性预测急性药物经验和药物使用结果。我们将首先研究光遗传技术 用于神经控制，以映射MDMA、甲基苯丙胺和氯胺酮对神经行为的影响 啮齿动物的风险和回报。其次，我们将使用神经成像来描绘急性和累积影响 这些药物对人类神经行为靶点的影响，侧重于风险和回报回路，并伴随 行为。我们还将评估这些药物暴露对神经行为目标的影响程度 预测未来6个月内的使用模式。第三，我们将把我们的方法扩展到 MDMA、甲基苯丙胺和氯胺酮对全脑的急性累积效应特征 连接性和相关行为，如控制程度。在这第三个目标下，我们将评估 在相同的随访期内对未来使用模式的预测。这一结果将推动我们的科学研究 了解为什么人们会有动机使用这些药物，并为未来提供基础 对量身定制的干预策略的调查。

SUMMARY MDMA (‘ecstasy’) and ketamine are drugs of abuse that have steadily gained in popularity. Compared to more traditional stimulants or narcotics, however, less is known about their mode of action, their subjective effects, and how these effects promote continued use. Our objective is to develop a theoretically-informed characterization of the effects of MDMA, methamphetamine and ketamine on the neurobehavior of specific circuits for processing risk and reward, the connectivity of these circuits, and how these circuits and their connectivity predict acute drug experience and drug use outcomes. We will first pursue optogenetic techniques for neural control to map the effects of MDMA, methamphetamine and ketamine on neurobehavior related to risk and reward in rodents. Second, we will use neuroimaging to map both the acute and cumulative influence of these drugs on neurobehavioral targets in humans, focusing on risk and reward circuits and accompanying behaviors. We will also assess the extent to which these influences of drug exposure on neurobehavioral targets predict future use patterns over a follow up period of 6 months. Third, we will extend our approach to characterizing the acute and cumulative effects of MDMA, methamphetamine and ketamine on whole brain connectivity and associated behaviors such as degree of control. Under this third objective we will assess the prediction of future use patterns over the same follow up period. The results will advance our scientific understanding about why people are motivated to use these drugs, and provide a foundation for future investigations of tailored intervention strategies.