Blockade of Dopamine D3 Receptors in the Ventral Tegmental Area Mitigates Fear Memory Generalization

The generalization of fear memories is an adaptive neurobiological process that promotes survival in complex and dynamic environments. While generalization has adaptive value, fear generalization is maladaptive and is a significant feature of stress-related disorders such as post-traumatic stress disorder (PTSD). The dopamine system plays a crucial role in both reward- and fear-related processes; however, the contribution of dopamine D3 receptors (D3Rs) to fear generalization in intense foot-shock models remains unclear. In this study, we administered a highly selective D3R antagonist, YQA14 (1 μg/0.2 μL/side), in the ventral tegmental area (VTA), which significantly inhibited fear generalization in novel contexts within foot-shock models. This effect was mediated by reducing the neuronal activity in the basolateral amygdala (BLA). These findings enhance our understanding of the neurobiology of generalization, which is essential from a translational perspective and has broad implications for treating generalized fear disorders.