A hallmark of anxiety disorders is the tendency to overgeneralize fear-related behaviors toward harmless stimuli or situations. But little is known about the factors contributing to overgeneralization. Here we investigated the role of acute stress and consolidation in promoting fear overgeneralization. Acute stress resulted in broad generalization of a conditioned fear memory, but only if stress occurred at least 24 h after memory formation. This finding shows that remote fear memories are more sensitive to the effects of stress than newly formed fear memories. Susceptibility to stress for old memories may be a contributing factor to overgeneralization in a host of anxiety and stress-related disorders.

Abstract

Stress broadly affects the ability to regulate emotions and may contribute to generalization of threat-related behaviors to harmless stimuli. Behavioral generalization also tends to increase over time as memory precision for recent events gives way to more gist-like representations. Thus, acute stress coupled with a delay in time from a negative experience may be a strong predictor of the transition from normal to generalized fear expression. Here, we investigated the effect of a single-episode acute stressor on generalization of aversive learning when stress is administered either immediately after an aversive learning event or following a delay. In a between-subjects design, healthy adult volunteers underwent threat (fear) conditioning using a tone-conditioned stimulus paired with an electric shock to the wrist and another tone not paired with shock. Behavioral generalization was tested to a range of novel tones either on the same day (experiment 1) or 24 h later (experiment 2) and was preceded by either an acute stress induction or a control task. Anticipatory sympathetic arousal [i.e., skin conductance responses (SCRs)] and explicit measures of shock expectancy served as dependent measures. Stress administered shortly after threat conditioning did not affect behavioral generalization. In contrast, stress administered following a delay led to heightened arousal and increased generalization of SCRs and explicit measures of shock expectancy. These findings show that acute stress increases generalization of older but not recent threat memories and have clinical relevance to understanding overgeneralization characteristics of anxiety and stress-related disorders.