Unpredictable stress boosts perceptual learning and alters glucocorticoid and norepinephrine receptors in rats’ dorsal hippocampus

Cumulative stress is known for its detrimental effects, including anxiety and stress-related disorders. However, the potential positive or 'hormetic' outcomes of chronic unpredictable stress (CUS) remain vague. In our study using adult male Wistar rats subjected to a 14-day CUS model, we explored the implications of its cumulative effects. We focused on how CUS influenced anxiety-like behavior, extinction memory, and the expression of specific receptors in the dorsal hippocampus (dHP). Our results indicated that CUS led to increased anxiety-related behaviors and heightened basal corticosterone levels. Interestingly, while aversive memory retrieval in CUS rats showed increased freezing, they exhibited enhanced memory extinction. This result suggests a compensatory mechanism initiated by CUS, allowing the rats to overcome the adverse effects of heightened freezing during memory recall. Moreover, during the extinction phase, there were notable changes in receptor expressions and neuronal activation in the dHP. Specifically, there was an increase in glucocorticoid receptor expression and a decrease in glutamate and adrenergic receptor expression levels. This altered receptor profile was linked to an overall rise in neuronal activity, albeit not immediate but cumulative. In summary, our findings indicate that while CUS amplifies anxiety-like behaviors, it paradoxically enhances specific cognitive processes. The altered receptor expression patterns in the dHP and increased neuronal activity suggest that CUS might provide individuals with improved coping mechanisms against recurring stressful situations, revealing stress responses' complex and sometimes beneficial nature.