Liu Juntong, Kou Juan, Tan Lisha, Li Hong, Lei Yi
College of Psychology, Shenzhen University, Shenzhen 518060, China; Center for Neurogenetics, Shenzhen Institute of Neuroscience, Shenzhen 518057, China.
Institution for Brain and Psychological Science, Sichuan Normal University, Chengdu 610066, China.
Psychoneuroendocrinology. 2025 Jun;176:107421. doi: 10.1016/j.psyneuen.2025.107421. Epub 2025 Mar 5.
Fear is an adaptive response that protects individuals from potential threats, but when excessive, it can lead to mental health disorders such as generalized anxiety disorder. Oxytocin is a neuromodulator whose effects on fear processing have been explored, although research results are inconsistent. Previous research indicates that administering oxytocin before fear acquisition can enhance fear learning, while studies have suggested a potential for reducing fear generalization when oxytocin is given after fear acquisition. However, few studies have explored the interplay between oxytocin-induced enhanced fear learning and its drug impact on fear generalization afterwards. To investigate this interaction, a double-blind, placebo-controlled study was conducted where oxytocin was administered before fear acquisition to assess its influence on fear generalization during the drug's effect. A total of 54 healthy male participants were recruited, with 29 in the experimental group and 25 in the control group. Participants received intranasal oxytocin 30 minutes before the fear acquisition phase, with the generalization phase occurring 45 minutes after the intranasal oxytocin. Results revealed that oxytocin increased shock expectancy ratings for fear stimuli (compared with safe stimuli) during acquisition and elevated shock expectancy for generalization stimuli in the generalization phase. These findings suggested that oxytocin may increase vigilance towards safe stimuli and contribute to maladaptive generalization when intranasal oxytocin was administered prior to fear acquisition. This study provides new insights into the potential clinical applications of oxytocin for interaction effect of oxytocin-induced enhanced fear learning to both fear acquisition and fear generalization fear-related disorders.
恐惧是一种适应性反应，可保护个体免受潜在威胁，但过度恐惧会导致心理健康障碍，如广泛性焦虑症。催产素是一种神经调节剂，其对恐惧处理的影响已得到研究，尽管研究结果并不一致。先前的研究表明，在恐惧习得前给予催产素可增强恐惧学习，而一些研究则表明，在恐惧习得后给予催产素有可能减少恐惧泛化。然而，很少有研究探讨催产素诱导的增强恐惧学习与其对随后恐惧泛化的药物影响之间的相互作用。为了研究这种相互作用，进行了一项双盲、安慰剂对照研究，在恐惧习得前给予催产素，以评估其在药物作用期间对恐惧泛化的影响。共招募了54名健康男性参与者，其中实验组29人，对照组25人。参与者在恐惧习得阶段前30分钟接受鼻内催产素，鼻内催产素后45分钟进入泛化阶段。结果显示，催产素在习得期间增加了对恐惧刺激（与安全刺激相比）的电击预期评分，并在泛化阶段提高了对泛化刺激的电击预期。这些发现表明，在恐惧习得前给予鼻内催产素时，催产素可能会增加对安全刺激的警惕性，并导致适应不良的泛化。这项研究为催产素在恐惧习得和恐惧泛化相关障碍中诱导增强恐惧学习的相互作用效应的潜在临床应用提供了新的见解。
