Exploring stress hormone effects on memory specificity and strength in mice using the dual-event inhibitory avoidance task

Abstract

Stressful and emotionally arousing experiences induce the release of noradrenergic and glucocorticoid hormones that synergistically strengthen memories but differentially regulate qualitative aspects of memory. This highlights the need for sophisticated behavioral tasks that allow for the assessment of memory quality. The dual-event inhibitory avoidance task for rats is such a behavioral task designed to evaluate both the strength and specificity of memory. The noradrenergic stimulant yohimbine given systemically immediately after the training session was found to enhance both the strength and specificity of memory, whereas the glucocorticoid corticosterone induced a generalized strengthening of memory. As mice are the preferred species for targeted gene and neural circuit manipulations, we here aimed to set up the dual-event inhibitory avoidance task for mice, and to replicate the effects of systemic yohimbine and corticosterone administration on memory strength and specificity. Whereas noninjected control mice efficiently acquired the task and selectively avoided the test context previously associated with footshock, the introduction of posttraining intraperitoneal injections induced testing order effects and substantially increased variability both within groups and across experiments, precluding a thorough investigation of stress hormone effects on memory specificity. Thus, whereas the dual-event inhibitory avoidance task can be used to test the specificity of memory in mice, our findings indicate that intraperitoneal injections impact performance. Therefore, this task is less suitable to assess stress hormone effects on memory specificity in mice.