Long-term effects of social stress on brain and behavior: a focus on hippocampal functioning

Abstract

In order to study mechanisms involved in the etiology of human affective disorders, there is an abundant use of various animal models. Next to genetic factors that predispose for psychopathologies, environmental stress is playing an important role in the etiology of these mental diseases. Since the majority of stress stimuli in humans that lead to psychopathology are of social nature, the study of consequences of social stress in experimental animal models is very valuable. The present review focuses on one of these models that uses the resident-intruder paradigm. In particular the long-lasting effects of social defeat in rats will be evaluated. Data from our laboratory on the consequences of social defeat on emotional behavior, stress responsivity and serotonergic functionality are presented. Furthermore, we will go into detail on hippocampal functioning in socially stressed rats. Very recent results show that there is a differential effect of a brief double social defeat and repetitive social defeat stress on dendritic remodeling in hippocampal CA3 neurons and that this has repercussions on hippocampal LTP and LTD. Both the structural and electrophysiological changes of principal neurons in the hippocampal formation after defeat are discussed as to their relationship with the maintenance in cognitive performance that was observed in socially stressed rats. The results are indicative of a large dynamic range in the adaptive plasticity of the brain, allowing the animals to adapt behaviorally to the previously occurred stressful situation with the progression of time.

Introduction

Stressful life events are generally considered as having precipitating effects on the development of human psychopathologies such as anxiety and clinical depression [1], [2], [3]. In order to study mechanisms involved in the etiology of these affective disorders, there is an abundant use of various animal models. This large variety in models used reflects Selye's concept of a core physiological response pattern to homeostatic challenges [4]. The effectiveness of stressors applied in these models to induce a pathology-like state that resembles a failing adaptive capacity, is dependent on the absence of the animal's possibilities to cope with the challenge [5]. Although large individual differences exist in the way animals as well as humans cope with stress [6], these coping strategies in general encompass adequate behavioral, physiological and neurobiological tools to diminish the impact of the stressor. Since the aim of many animal stress models is to mimic human stress-related psychopathologies, researchers aim at inducing a state in the experimental animals that bears an obvious resemblance to the behavioral or physiological signs of these clinical disorders. In order to reach this state, frequently stressors are applied with a relatively high intensity that have a chronic character. Usually, the behavioral, physiological and neurobiological consequences are studied during or shortly after the end of the stress period. Only few studies focused on longer-lasting, persisting effects of this prolonged stress exposure. There appears to be, however, a growing interest in the study of long-term behavioral and physiological consequences of short-lasting, episodic-like stressors, which will be the focus of this review.