The complex role of oxytocin in fear acquisition and generalization

Abstract

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.