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

National Institute On Drug Abuse

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Abstract

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.