Behavioral and physiological characterization of male mice under chronic psychosocial stress (original) (raw)

A model of social stress in dominant mice

Physiology & Behavior, 2001

The possibility of socially stressing the dominant/aggressive member of a pair of male mice is tested. Male mice (NMRI outbreed strain) were housed in pairs to assess dominant and subordinate roles by agonistic interactions and urine-marking test. Social stress for dominant males consisted in 30 min/day of exposure to their subordinate partner interacting with a female in the adjacent compartment of the cage, for 9 days. Results showed that dominance status was maintained. Behavioural observations indicated that neither the subordinates nor the dominant males habituated to this experimental procedure. At the end of the chronic stress, dominant animals were given the opportunity to interact for 30 min with a female in their compartment. Results indicated that stressed dominants showed impairment in their sexual behaviour and were more oriented towards the physical environment in comparison with control dominants. The behavioural response to apomorphine (0.25 mg/kg) indicated an alteration of the dopaminergic functioning in socially stressed dominant mice. This study suggests that the characteristics of the stressor and the effects of the chronic social stress could be different, according to male social status.

Fano, E., Sanchez-Martin, J.R., Arregi, A., Castro, B., Alonso, A., Brain, P. and Azpiroz, A. (2001). Social stress paradigms in male mice: Variations in behavior, stress and immunology. Physiology and Behavior 73: 165-173.

Physiology & Behavior, 2001

Male OF1 strain mice were allocated, after 2 weeks of individual housing, to cohabitating (6 or 16 days), fixed dyadic interaction pairs (6 or 16 daily encounters) or control groups (6 or 16 days). These different social stress situations were assessed for their effects on splenic contents of NE, IL-1 and IL-2 and serum levels of corticosterone. Spleen NE contents showed no significant variations, but serum corticosterone titers were generally higher in interacting pairs and subordinates. Splenic IL-2 did not respond in the same way to the treatments as IL-1. The differences in splenic interleukin contents could not be simply related to observed changes in serum corticosterone levels. Different mechanisms appear to regulate changes in glucocorticoids and the measured cytokines. These physiological phenomena do not simply reflect in the animal's social status (dominant or submissive). The intensity and duration of the agonistic behavior displayed as well as the interaction experience accumulated may account for the observed differences between the paradigms.

Neuroendocrine and neurochemical impact of aggressive social interactions in submissive and dominant mice: implications for stress-related disorders

The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2010

Social conflicts may engender stress-related behavioural and physiological disturbances in the victims of aggression. In addition, stress-like neurochemical changes and ensuing depressive and anxiety symptoms might also be evident in the perpetrators of aggressive acts. The present investigation assessed basal levels of circulating corticosterone and of brain serotonin (5-HT) and norepinephrine (NE) in pre-identified submissive and dominant mice. In addition, brain neurochemical changes were determined following a single or three 15-min aggressive episodes both in submissive mice and in those that dominated the aggressive interplay. Three minutes after single and repeated confrontations, plasma corticosterone levels and 5-HT utilization within the prefrontal cortex (PFC) and hippocampus were increased to a comparable extent in submissive and dominant animals. Interestingly, however, NE utilization within the PFC and hippocampus was augmented to a greater level in submissive mice. Th...

Social stress paradigms in male mice: Variations in behavior, stress and immunology

Physiology & Behavior, 2001

Male OF1 strain mice were allocated, after 2 weeks of individual housing, to cohabitating (6 or 16 days), fixed dyadic interaction pairs (6 or 16 daily encounters) or control groups (6 or 16 days). These different social stress situations were assessed for their effects on splenic contents of NE, IL-1 and IL-2 and serum levels of corticosterone. Spleen NE contents showed no significant variations, but serum corticosterone titers were generally higher in interacting pairs and subordinates. Splenic IL-2 did not respond in the same way to the treatments as IL-1. The differences in splenic interleukin contents could not be simply related to observed changes in serum corticosterone levels. Different mechanisms appear to regulate changes in glucocorticoids and the measured cytokines. These physiological phenomena do not simply reflect in the animal's social status (dominant or submissive). The intensity and duration of the agonistic behavior displayed as well as the interaction experience accumulated may account for the observed differences between the paradigms.

Social Instability is an Effective Chronic Stress Paradigm for both Male and Female Mice

2019

ABSTRACTDespite stress-associated disorders having a higher incidence rate in females, preclinical research mainly focuses on males. Chronic stress paradigms, such as chronic social defeat and chronic corticosterone administration, were mainly designed and validated in males and subsequent attempts to use these paradigms in females has demonstrated sex differences in the behavioral and HPA axis response to stress. Here, we developed a social stress paradigm, social instability stress (SIS), which exposes adult mice to unstable social hierarchies for 7 weeks. SIS effectively induces negative valence behaviors and hypothalamus-pituitary-adrenal (HPA) axis activation in both males and females. Importantly, while there were effects of estrous cycle on behavior, this variability did not impact the overall effects of SIS on behavior, suggesting estrous does not need to be tracked while utilizing SIS. Furthermore, the effects of SIS on negative valence behaviors were also reversed followin...

The differential impact of social defeat on mice living in isolation or groups in an enriched environment: plasma corticosterone and monoamine variations

International Journal of Neuropsychopharmacology, 2012

Social defeat in mice is a potent stressor that promotes the development of depressive- and anxiety-like behaviours, as well as variations of neuroendocrine and brain neurotransmitter activity. Although environmental enrichment may protect against some of the adverse behavioural and biological effects of social defeat, it seems that, among male group-housed mice maintained in an enriched environment (EE), aggressive behaviours may be more readily instigated, thus promoting distress and exacerbating psychopathological features. Thus, although an EE can potentially have numerous beneficial effects, these may depend on the general conditions in which mice were raised. It was observed in the current investigations that EE group-housed BALB/cByJ mice displayed increased anxiety-like behaviours compared to their counterparts maintained in a standard environment (SE). Furthermore, in response to social defeat, EE group-housed male mice exhibited decreased weight gain, exaggerated corticost...

The physiology of social conflict in rats: What is particularly stressful?

Behavioral Neuroscience, 1996

The involvement of the opponent's behavior in the aggression-induced stress response was tested. Subjects (male Wistar rats) faced stimulus rats previously submitted either to mediobasal hypothalamic lesion (MBHL) or to sham operation. MBHL intruders were more aggressive but were also more ready to submit compared with sham-operated rats; as residents they were more efficient in inducing submissive behavior in the opponent. The subject's stress response at 15 min was neither dependent on the intensity of aggressive behavior nor on residence status but on dominant-submissive relationships. The submission of the stimulus rat reduced corticosterone plasma levels in the subjects, while the subjects' own submissive behavior elicited a very significant increase in its plasma corticosterone. In contrast, plasma glucose seemed to depend on residence status, whereas plasma free fatty acids reacted to any novel event (including cage switch).

Acute and chronic restraint stress alter the incidence of social conflict in male rats

Hormones and Behavior, 2003

Stress and elevated stress hormone levels are known to alter cognition, learning, memory, and emotional responses. Three weeks of chronic stress or glucocorticoid exposure is reported to alter neuronal morphology in the hippocampus, the amygdala, and the prefrontal cortex, and to decrease neurogenesis in the dentate gyrus. Here we examine the effects of acute and chronic restraint stress exposure on the incidence of emotional responses throughout a 3-week period among adult rat conspecifics. Our data indicate that acute restraint stress (i.e., a single 6-h exposure) results in a significant reduction in aggressive conflicts among stressed males compared to experimental controls. In contrast, on Days 14 and 21, repeatedly restrained rats exhibited significantly more aggressive behaviors than controls. Blood samples taken 18 h after the last restraint session indicate that plasma concentrations of the stress hormone corticosterone (CORT) in stressed rats were equivalent to those of unstressed rats; however, the number of individually initiated aggressive acts observed positively correlated with plasma CORT measures taken at the end of the study. In contrast to studies of psychosocial stress or intruder paradigms, here we observe spontaneous emotional responses to an uncontrollable stressor in the homecage. This study provides a novel examination of the effects of chronic restraint stress on emotional responses in the home environment among cagemates. These results indicate that acute and chronic restraint stress alter the incidence of aggression, and emphasize the relevance of this model of chronic stress to studies of stress-responsive disorders characterized by aggressive behavior.

Time matters: pathological effects of repeated psychosocial stress during the active, but not inactive, phase of male mice

Journal of Endocrinology, 2012

Recent findings in rats indicated that the physiological consequences of repeated restraint stress are dependent on the time of day of stressor exposure. To investigate whether this is also true for clinically more relevant psychosocial stressors and whether repeated stressor exposure during the light phase or dark phase is more detrimental for an organism, we exposed male C57BL/6 mice to social defeat (SD) across 19 days either in the light phase between Zeitgeber time (ZT)1 and ZT3 (SDL mice) or in the dark phase between ZT13 and ZT15 (SDD mice). While SDL mice showed a prolonged increase in adrenal weight and an attenuated adrenal responsiveness to ACTH in vitro after stressor termination, SDD mice showed reduced dark phase home-cage activity on observation days 7, 14, and 20, flattening of the diurnal corticosterone rhythm, lack of social preference, and higher in vitro IFNg secretion from mesenteric lymph node cells on day 20/21. Furthermore, the colitis-aggravating effect of SD was more pronounced in SDD than SDL mice following dextran sulfate sodium treatment. In conclusion, the present findings demonstrate that repeated SD effects on behavior, physiology, and immunology strongly depend on the time of day of stressor exposure. Whereas physiological parameters were more affected by SD during the light/inactive phase of mice, behavioral and immunological parameters were more affected by SD during the dark phase. Our results imply that repeated daily SD exposure has a more negative outcome when applied during the dark/active phase. By contrast, the minor physiological changes seen in SDL mice might represent beneficial adaptations preventing the formation of those maladaptive consequences. Journal of Endocrinology 215, 425-437 severity. Data represent meanCS.E.M.; *P%0 . 05 vs respective SHC mice; C P!0 . 05 vs respective SDL mice. Pathological effects of social defeat are dependent on the time of day . M S BARTLANG and others 433

Behavioural, physiological and immunological consequences of social status and aggression in chronically coexisting resident-intruder dyads of male rats

Physiology & behavior, 1986

The behavioural and physiological consequences of social status and reciprocal fighting in resident-intruder dyads of Long Evans male rats were evaluated. Before a chronic cohabitation of 10 days, residents and intruders were individually housed for one month to increase their aggressiveness. Control animals included isolates, i.e., animals kept individually housed throughout the experiment and pair-housed rats, i.e., pairs of rats housed together from their rats in the laboratory. In 19 out of 20 dyads, a clear dominance relationship developed with an advantage to the resident in 68% of the cases. Dominants showed more exploratory activity than subordinates in a open-field test at the end of the cohabitation period; subordinates groomed longer than animals from other experimental groups. Dominants had lower pain thresholds than individually and pair-housed animals. Both dominants and subordinates had higher tyrosine hydroxylase enzymatic activities in the left adrenal than isolated...