Multimodal preclinical imaging studies of decisional determinants of drug vs non-drug choice

最有效的成瘾治疗之一是应急管理，其中提供替代奖励以换取戒断。我们通过使用触摸屏在实验室动物中建立经济选择来模拟这种方法，触摸屏显示数量表示刺激并检测选择反应。动物所做选择的经济性质通过饱食导致的牛奶奖励贬值或通过盐水替代的药物（瑞芬太尼）奖励来验证。为了操纵特定的电路，我们正在与其他实验室合作开发聚焦超声刺激方法，以及灵长类动物的化学遗传工具箱，可以在临床上建立其潜在的应用。 过去一年的进展包括建立高分辨率清醒非人类灵长类动物PET成像，并开始调查新出现的聚焦超声操纵神经组织。当我们完善这种方法时，清醒PET研究将用于帮助表征使用18F-氟脱氧葡萄糖测量局部相对脑代谢率对定义的神经系统的影响。 互补的研究将建立在最近接受的文件中，我们模型的应急管理方法与强加的“审议”模式的处理，我们对比的“立即冲动”的处理模式。这两种模式将在清醒PET研究期间以块对比设计进行对比。

One of the most effective addiction treatments is contingency management, in which alternate rewards are offered in exchange for abstention. We model this approach by establishing economic choice in lab animals using touch screens that display quantity signifying stimuli and detect choice responses. The economic nature of the choices animals make was verified by devaluation of milk reward through satiation, or drug (remifentanil) reward through saline substitution. To manipulate specific circuits, we are collaborating with other labs to develop focused ultrasound stimulation approaches, as well as a chemogenetic toolbox for primates that could establish their potential application in the clinic. Progress in the past year includes establishing high resolution awake nonhuman primate PET imaging, and initiation of investigation of newly emerging focused ultrasound manipulations of neural tissue. As we refine this approach, the awake PET studies will be used to help characterize effects on defined neural systems using 18F-fluorodeoxyglucose to measure localized relative cerebral metabolic rate. Complimentary studies will build upon a recently accepted paper in which we model contingency management approaches with an imposed "deliberative" mode of processing, which we contrast with an "immediate impulsive" mode of processing. These two modes will be contrasted during awake PET studies in a block contrast design.