Differential effects of chronic stress on memory processes in the tree shrew

Unpredictable and uncontrollable stressful events have been shown to affect cognitive processes. Interestingly, only hippocampus-mediated memory processes are thought to be sensitive to the effects of chronic stress. In contrast, the hippocampus-independent memory processes have been shown to be resistant to chronic stressful experiences. A central feature of the stress response is the activation of the hypothalamus-pituitary-adrenocortical (HPA)-axis, resulting in increased plasma levels of glucocorticoids, and several studies suggested that the performance of hippocampus-mediated memory processes might be directly modulated by these adrenal steroids. We investigated the impact of chronic psychosocial stress on hippocampus-mediated and hippocampus-independent memory processes in male tree shrews. By using a modified holeboard we followed memory performance during 23 weeks of alternating stress-free and stressful conditions. This schedule was designed to mimic a more realistic situation with stress-free conditions being sequentially interrupted by challenging events. The results indicate that chronic stress differentially affects hippocampus-mediated and hippocampus-independent memory processes in tree shrews. While hippocampus-independent memory processes remained unimpaired throughout the study, hippocampus-mediated memory was persistently impaired, not only during stress periods but also during recovery periods. This persistent impairment seems not to be exclusively triggered by glucocorticoids because urinary free cortisol concentration returned to normal during recovery periods. The present study is the first to evaluate the consequences of sequential stress exposure on memory performance in animals. Apparently, the mechanisms modulating cognitive processes are far from being understood and need a very systematic analysis in animal models with a high face and predictive validity to human stress-related memory disorders.