The Role of Accumbal Dopamine in Shaping Adaptive and Maladaptive Aversive Learning Strategies

Abstract

How an animal navigates an environment is critical for its survival, requiring it to avoid threats while approaching resources such as food, warmth, and shelter. This adaptive behavior depends on cue–response and cue–outcome associations that allow animals to determine when aversive events are avoidable versus uncontrollable; a distinction that is often disrupted in stress-related disorders such as post-traumatic stress and anxiety disorders. Dopamine release in the nucleus accumbens (NAc) core supports the formation of these associations to promote adaptive behavior, and dysregulated signaling in this region is linked to maladaptive learning and psychiatric disorders. In this work, mice performed a negative reinforcement task in which a discriminative cue signaled an opportunity to perform an operant response (lever press) to avoid or terminate a series of footshocks. Using fiber photometry and the optical sensor dLight, dopamine dynamics were tracked across training in the NAc core as animals either acquired active avoidance or remained passive, resembling learned helplessness. A trial-termination cue that indicated shock cessation evoked a robust phasic dopamine transient that was selectively heightened in mice that went on to adopt an active avoidance strategy. This action-linked dopamine signal emerged before mice behaviorally diverged and predicted the acquisition of an active avoidance strategy. Its amplitude declined over training, specifically in conditions where the operant response produced the cue presentation, consistent with a teaching signal that updated as contingencies were learned. However, this signal did not align with the encoding of reward, safety, or classical reward prediction error. Dopamine signaling to the trial-termination cue tracked the salience of this event early in learning and updated with behavior across multiple task conditions. Furthermore, causal manipulations of dopamine release in the NAc confirmed that heightened dopamine at the action-dependent trial-termination cue promoted adaptive learning strategies. Overall, these findings identify a dopamine-driven, agency-dependent mechanism for updating cue–outcome associations during negative reinforcement and show how control over outcomes shapes learning. This mechanism provides a framework for understanding how dopaminergic dysfunction may contribute to maladaptive passivity and perceived uncontrollability in stress-related psychiatric disorders.