Linking cognitive abilities and stress reactivity: insights from the HR/IR/LR mouse model

Abstract

Multiple effects of stress hormones on learning and memory have been described, revealing both facilitating and impairing influences of glucocorticoids. Moreover, performance in social and spatial memory tasks largely depend on brain structures also involved in HPA axis regulation and behavioural emotionality. Among depressive patients, dysfunctions of the stress hormone system as well as decreased cognitive abilities are frequently observed. Mimicking a neuroendocrine core symptom of depression, the HR/IR/LR mouse model was established by selectively breeding mice according to the trait of high (HR), intermediate (IR) and low (LR) stress reactivity, respectively. Investigating the animals cognitive performance, two distinct learning tasks, the Y-maze test and the social discrimination (SD) test, were performed. In the SD test, IR animals showed the best learning/memory results. As expected, cognitive deficits in social memory were found in the two depression-associated mouse lines (HR and LR). In the Y-maze test, however, LR mice showed a superior ability to remember spatial cues. Accumulatively increased hippocampal corticosterone exposure in HR animals is probably responsible for this reduction in spatial learning performance. Thus, our results confirm that the phenotype of hyper- and hypo-reactivity to stressors is accompanied by context-dependent alterations of cognitive abilities, rendering the HR/IR/LR mouse lines a promising animal model for depressive disorders.