NEUROBEHAVIORAL MEASUREMENTS OF NATURAL AND OPIOID REWARD VALUE

OF DISSERTATION NEUROBEHAVIORAL MEASUREMENTS OF NATURAL AND OPIOID REWARD VALUE In the last decade, (non)prescription opioid abuse, opioid use disorder (OUD) diagnoses, and opioid-related overdoses have risen and represent a significant public health concern. One method of understanding OUD is as a disorder of choice that requires choosing opioid rewards at the expense of other nondrug rewards. The characterization of OUD as a disorder of choice is important as it implicates decisionmaking processes as therapeutic targets, such as the valuation of opioid rewards. However, reward-value measurement and interpretation are traditionally different in substance abuse research compared to related fields such as economics, animal behavior, and neuroeconomics and may be less effective for understanding how opioid rewards are valued. The present research therefore used choice procedures in line with behavioral/neuroeconomic studies to determine if drug-associated decision making could be predicted from economic choice theories. In Experiment 1, rats completed an isomorphic food-food probabilistic choice task with dynamic, unpredictable changes in reward probability that required constant updating of reward values. After initial training, the reward magnitude of one choice subsequently increased from one to two to three pellets. Additionally, rats were split between the Signaled and Unsignaled groups to understand how cues modulate reward value. After each choice, the Unsignaled group received distinct choice-dependent cues that were uninformative of the choice outcome. The Signaled group also received uninformative cues on one option, but the alternative choice produced reward-predictive cues that informed the trial outcome as a win or loss. Choice data were analyzed at a molar level using matching equations and molecular level using reinforcement learning (RL) models to determine how probability, reward magnitude, and reward-associated cues affected choice. Experiment 2 used an allomorphic drug versus food procedure where the food reward for one option was replaced by a self-administered remifentanil (REMI) infusion at doses of 1, 3 and 10 μg/kg. Finally, Experiment 3 assessed the potential for both REMI and food reward value to be commonly scaled within the brain by examining changes in nucleus accumbens (NAc) Oxygen (O2) dynamics. Results showed that increasing reward probability, magnitude, and the presence of reward-associated cues all independently increased the propensity of choosing the associated choice alternative, including REMI drug choices. Additionally, both molar matching and molecular RL models successfully parameterized rats’ decision dynamics. O2 dynamics were generally commensurate with the idea of a common value signal for REMI and food with changes in O2 signaling scaling with the reward magnitude of REMI rewards. Finally, RL model-derived reward prediction errors significantly correlated with peak O2 activity for reward delivery, suggesting a possible neurological mechanism of value updating. Results are discussed in terms of their implications for current conceptualizations of substance use disorders including a potential need to change the discourse surrounding how substance use disorders are modeled experimentally. Overall, the present research provides evidence that a choice model of substance use disorders may be a viable alternative to the disease model and could facilitate future treatment options centered around economic principles.