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The nucleus accumbens (NAc) is a key node within corticolimbic circuitry for guiding action selection and cost/benefit decision making in situations involving reward uncertainty. Preclinical studies have typically assessed risk/reward decision making using assays where decisions are guided by internally generated representations of choice-outcome contingencies. Yet, real-life decisions are often influenced by external stimuli that inform about likelihoods of obtaining rewards. How different subregions of the NAc mediate decision making in such situations is unclear. Here, we used a novel assay colloquially termed the "Blackjack" task that models these types of situations. Male Long-Evans rats were trained to choose between one lever that always delivered a one-pellet reward and another that delivered four pellets with different probabilities [either 50% (good-odds) or 12.5% (poor-odds)], which were signaled by one of two auditory cues. Under control conditions, rats selected the large/risky option more often on good-odds versus poor-odds trials. Inactivation of the NAc core caused indiscriminate choice patterns. In contrast, NAc shell inactivation increased risky choice, more prominently on poor-odds trials. Additional experiments revealed that both subregions contribute to auditory conditional discrimination. NAc core or shell inactivation reduced Pavlovian approach elicited by an auditory CS+, yet shell inactivation also increased responding during presentation of a CS-. These data highlight distinct contributions for NAc subregions in decision making and reward seeking guided by discriminative stimuli. The core is crucial for implementation of conditional rules, whereas the shell refines reward seeking by mitigating the allure of larger, unlikely rewards and reducing expression of inappropriate or non-rewarded actions. SIGNIFICANCE STATEMENT Using external cues to guide decision making is crucial for adaptive behavior. Deficits in cue-guided behavior have been associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder and schizophrenia, which in turn has been linked to aberrant processing in the nucleus accumbens. However, many preclinical studies have often assessed risk/reward decision making in the absence of explicit cues. The current study fills that gap by using a novel task that allows for the assessment of cue-guided risk/reward decision making in rodents. Our findings identified distinct yet complementary roles for the medial versus lateral portions of this nucleus that provide a broader understanding of the differential contributions it makes to decision making and reward seeking guided by discriminative stimuli.

Differential Contributions of Nucleus Accumbens Subregions to Cue-Guided Risk/Reward Decision Making and Implementation of Conditional Rules