Project 4

总结 MDMA（'摇头丸'）和氯胺酮是滥用药物，已稳步增长的普及。相比于更 然而，对于传统的兴奋剂或麻醉剂，人们对它们的作用方式，它们的主观效果， 以及这些影响如何促进持续使用。我们的目标是发展一个理论上知情的 MDMA，甲基苯丙胺和氯胺酮对特定神经行为的影响的特征 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。我们将首先采用光遗传学技术 用于神经控制，以绘制MDMA、甲基苯丙胺和氯胺酮对与以下相关的神经行为的影响： 啮齿动物的风险和回报其次，我们将使用神经成像来绘制急性和累积影响， 这些药物对人类神经行为目标的影响，重点是风险和回报回路， 行为。我们还将评估药物暴露对神经行为目标的影响程度 在6个月的随访期内预测未来的使用模式。第三，我们将扩大我们的做法， 描述MDMA、甲基苯丙胺和氯胺酮对全脑的急性和累积效应 连接性和相关行为，如控制程度。在第三个目标下，我们将评估 预测同一随访期内的未来使用模式。这些结果将推动我们的科学 了解为什么人们有动机使用这些药物，并为未来的研究奠定基础。 调查有针对性的干预战略。

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.