Simple SummaryUnderstanding how stress impacts fear learning can provide important insight into the etiology of stress-related psychological disorders, such as post-traumatic stress disorder (PTSD). Thus, we exposed healthy participants to a brief stressor 30 min prior to a learning task in which one visual stimulus (CS+), but not another (CS−), was associated with an aversive airblast to the throat. The next day, we quantified participants’ fear in response to the CS+, CS−, and several visual stimuli that had never been observed by participants. Our results indicated that stress impaired the acquisition of fear on Day 1, particularly in participants who exhibited the greatest cortisol responses to stress. Contrary to expectations, pre-learning stress did not significantly influence the generalization of fear measured on Day 2. Our findings suggest that stress, perhaps through increased cortisol levels, alters the acquisition of fear. This may be useful in understanding the distortion of fear memories in stress-related disorders.AbstractFew studies have examined the time-dependent effects of stress on fear learning. Previously, we found that stress immediately before fear conditioning enhanced fear learning. Here, we aimed to extend these findings by assessing the effects of stress 30 min prior to fear conditioning on fear learning and fear generalization. Two hundred and twenty-one healthy adults underwent stress (socially evaluated cold pressor test) or a control manipulation 30 min before completing differential fear conditioning in a fear-potentiated startle paradigm. One visual stimulus (CS+), but not another (CS−), was associated with an aversive airblast to the throat (US) during acquisition. The next day, participants were tested for their fear responses to the CS+, CS−, and several generalization stimuli. Stress impaired the acquisition of fear on Day 1 but had no significant impact on fear generalization. The stress-induced impairment of fear learning was particularly evident in participants who exhibited a robust cortisol response to the stressor. These findings are consistent with the notion that stress administered 30 min before learning impairs memory formation via corticosteroid-related mechanisms and may help us understand how fear memories are altered in stress-related psychological disorders.