Fang Xiangjun, Ding Xiaoyan, Wu Ning, Li Jin, Song Rui
Nanjing University of Chinese Medicine, Nanjing 210029, China.
Academy Military Medical Sciences, 27th Taiping Road, Beijing 100850, China.
Int J Mol Sci. 2025 Jul 7;26(13):6520. doi: 10.3390/ijms26136520.
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.
恐惧记忆的泛化是一种适应性神经生物学过程，可促进在复杂多变环境中的生存。虽然泛化具有适应性价值，但恐惧泛化是适应不良的，并且是创伤后应激障碍（PTSD）等应激相关障碍的一个重要特征。多巴胺系统在奖赏和恐惧相关过程中都起着关键作用；然而，多巴胺D3受体（D3R）在强烈足部电击模型中对恐惧泛化的作用仍不清楚。在本研究中，我们在腹侧被盖区（VTA）给予了一种高度选择性的D3R拮抗剂YQA14（1μg/0.2μL/侧），这显著抑制了足部电击模型中在新环境下的恐惧泛化。这种效应是通过降低基底外侧杏仁核（BLA）中的神经元活动介导的。这些发现增进了我们对泛化神经生物学的理解，这从转化医学角度来看至关重要，并且对治疗广泛性恐惧障碍具有广泛意义。
