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.

Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers

“…In R animals, the decrease in hippocampal BDNF concentrations associated with hippocampal morphological changes is consistent with the depressive phenotype described in humans (Sheline et al, 1999;Bremner et al, 2000;Duman and Monteggia, 2006;Pittenger and Duman, 2008). Animal models of depression and psychosocial stress are associated with reduced hippocampal neurogenesis, hippocampal dendritic arborization, and hippocampal BDNF that are prevented by antidepressant treatment (Watanabe et al, 1992;Magariños et al, 1996Magariños et al, , 2011Sapolsky, 2000;Czeh et al, 2001;Buwalda et al, 2005;Yap et al, 2006;Castrén et al, 2007;Czeh and Lucassen, 2007;Becker et al, 2008;Krishnan and Nestler, 2008;Alleva and Francia, 2009;Covington et al, 2009). Depending on studies, the hippocampal spine density is or not affected by stress events (Chen et al, 2010;Magariños et al, 2011).…”

The delayed effects of chronic unpredictable stress on anxiety measures

“…Of particular interest would be to understand how chronic unpredictable stress alters brain regions and neurotransmitters thought to participate in stress activation and anxiety behaviors. Previous studies have found that structural remodeling of neurons in the dorsal hippocampus and basolateral amygdala persists for 3 weeks following termination of chronic restraint stress, as does increased anxietylike behaviors [7,31,57,59]. Unpredictable stress exposure did not result in similar structural or immediate behavioral changes, which may suggest that different neural substrates mediate the increase in anxiety behaviors following predictable compared to unpredictable stress [57,58].…”

“…Rats exposed to 7 days of unpredictable stress and tested 7 days later in the elevated plus-maze or a novel environment showed increased anxiety-like behaviors [13]. Single or multiple experiences of exposure to a predator, predator odor or social defeat augmented anxiogenic responses in rodents when tested 1 to 21 days following the exposure episode [1,2,4,5,7,8,11,45]. The sustained effects of predator stress have been reported in several unconditioned response tasks, including the elevated plusmaze and light-dark box [1][2][3]5,8].…”

“…Exposure of rodents to unpredictable stress has resulted in behavioral profiles indicative of human psychopathology [7,14,61,63]. Several chronic stress procedures have been published that use different stressors, 1-2 times per day for 7-54 days to model long-term human stress exposure [14,33,50,62,63].…”

“…Although the unpredictable stress procedures have been suggested as appropriate animal models of anxiety disorders due to their behavioral effects, these behavioral effects have not been measured after the cessation of the stress procedure [14,58]. Previous research with chronic predictable or single stress exposure reported an increase in anxiety measures 1-3 weeks following the last stress exposure [4,7,19,30,32,54,55,59]. Therefore, to systematically investigate the delayed effects of chronic unpredictable stress (CUS), the current study exposed rats to 10 days of unpredictable stress and then assessed anxiety on several behavioral measures 1, 7 or 14 days following the last stress exposure.…”