A dopamine-dependent mechanism for reward-induced modification of fear memories

How positive and negative affective stimuli interact in the brain to influence behavioral outcomes remains poorly understood. Here, we show that recall of a positive reward-associated conditioned stimulus (CSRew+) can prevent or reverse fear generalization in mice. Modification of generalized fear by recall of a CSRew+ is dependent on the midbrain dopamine system and the regulation of discriminatory threat encoding by the central amygdala (CeA). Precisely timed, transient elevations in dopamine and activation of dopamine D2 receptors in the CeA are necessary to reverse threat generalization and non-discriminatory threat encoding in the CeA. Recall of a positive association is also effective at enhancing the extinction of a conditioned threat response in a dopamine dependent manner. These data demonstrate that recall of a positive experience can be an effective means to suppress generalized fear and show that dopamine projections to the CeA are an important neural substrate for this phenomenon.