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

National Institute On Drug Abuse

Investigators

Linked publications, trials & patents

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 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. 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 as well as neurotransmitter-specific ligands such as 18F-DOPA to assess activity the dopaminergic system. A manuscript on these results is in development. In additional studies, we are developing an animal model of negative reinforcement, a major driving force in human addiction, to examine activated brain regions using PET imaging as described above. Prior studies attempting to develop rodent models of negative reinforcement have not been successful.