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

最有效的成瘾治疗方法之一是应急管理，即提供替代奖励以换取戒除毒瘾。我们通过使用触摸屏在实验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。动物做出的选择的经济性质通过通过饱腹来降低牛奶奖励或通过盐水替代来降低药物（瑞芬太尼）奖励来验证。为了控制特定的电路，我们正在与其他实验室合作开发聚焦超声刺激方法，以及用于灵长类动物的化学遗传学工具箱，以建立它们在临床中的潜在应用。

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.