Increased fear generalization results in reduced generalization of extinction

Abstract

Generalization of conditioned fear is adaptive for survival. However, overgeneralization of fear from threat cues to loosely similar yet safe stimuli is a hallmark of anxiety-related disorders. Such overgeneralization may impact other fear learning processes. In particular, broad fear generalization might limit the effectiveness of extinction training, which may further maintain anxiety. Here, we examined if increased generalization of conditioned fear might reduce the later generalization of fear extinction. To this end, we compared rats conditioned with moderate-versus high-intensity footshocks, the latter showing stronger generalization of acquired fear than the former. Within each shock intensity group, we then conducted extinction training using the original conditioned stimulus (CS) for half of the animals and a generalization stimulus (GS) for the others. We found stronger preserved responding to the CS after GS extinction in rats that had initially been conditioned using the high-intensity footshock than in rats conditioned using the moderate-intensity footshock, in line with the notion of reduced generalization of extinction from the GS to the CS in the former group. However, we also found indications for weaker retention of GS extinction in rats conditioned with the high-intensity footshock, which may in part or in whole explain the apparent difference in generalization of GS extinction to the CS. Our results may be important to consider in extinction-based exposure therapy, where patients often present with broadly generalized fears and exposure treatment is usually not conducted using the exact cues or situations for which fear was initially acquired. Highlights- We see greater CS-to-GS fear generalization using a strong (vs moderate) US in rats - Paradoxically, we see more preserved CS fear upon GS extinction in the former group - This may reflect an effect on extinction generalization and/or extinction retention - CS extinction reduced GS fear similarly in both groups - Male rats showed higher freezing during acquisition and extinction than females