Consequences Of Social Defeat Stress Research Articles

Fighting Females: Neural and Behavioral Consequences of Social Defeat Stress in Female Mice

BackgroundDespite the twofold higher prevalence of major depressive and posttraumatic stress disorders in women compared with men, most clinical and preclinical studies have focused on male subjects. We used an ethological murine model to study several cardinal symptoms of affective disorders in the female targets of female aggression. MethodsIntact Swiss Webster (CFW) female resident mice were housed with castrated male mice and tested for aggression toward female intruders. For 10 days, aggressive CFW female residents defeated C57BL/6J (B6) female intruders during 5-minute encounters. Measures of corticosterone, c-Fos activation in hypothalamic and limbic structures, and species-typical behaviors were collected from defeated and control females. Ketamine (20 mg/kg) was tested for its potential to reverse stress-induced social deficits. ResultsHoused with a castrated male mouse, most intact resident CFW females readily attacked unfamiliar B6 female intruders, inflicting >40 bites in a 5-minute encounter. Compared with controls, defeated B6 females exhibited elevated plasma corticosterone and increased c-Fos activation in the medial amygdala, ventral lateral septum, ventromedial hypothalamus, and hypothalamic paraventricular nucleus. Chronically defeated females also showed vigilance-like behavior and deficits in social interactions, novel object investigation, and nesting. The duration of social interactions increased 24 hours after chronically defeated female mice received a systemic dose of ketamine. ConclusionsThese findings demonstrate that CFW female mice living with male conspecifics can be used as aggressive residents in an ethological model of female social defeat stress. These novel behavioral methods will encourage further studies of sex-specific neural, physiological, and behavioral adaptations to chronic stress and the biological bases for interfemale aggression.

Social defeat stress: Mechanisms underlying the increase in rewarding effects of drugs of abuse.

Social interaction is known to be the main source of stress in human beings, which explains the translational importance of this research in animals. Evidence reported over the last decade has revealed that, when exposed to social defeat experiences (brief episodes of social confrontations during adolescence and adulthood), the rodent brain undergoes remodeling and functional modifications, which in turn lead to an increase in the rewarding and reinstating effects of different drugs of abuse. The mechanisms by which social stress cause changes in the brain and behavior are unknown, and so the objective of this review is to contemplate how social defeat stress induces long-lasting consequences that modify the reward system. First of all, we will describe the most characteristic results of the short- and long-term consequences of social defeat stress on the rewarding effects of drugs of abuse such as psychostimulants and alcohol. Secondly, and throughout the review, we will carefully assess the neurobiological mechanisms underlying these effects, including changes in the dopaminergic system, corticotrophin releasing factor signaling, epigenetic modifications and the neuroinflammatory response. To conclude, we will consider the advantages and disadvantages and the translational value of the social defeat stress model, and will discuss challenges and future directions.

Exploring the consequences of social defeat stress and intermittent ethanol drinking on dopamine dynamics in the rat nucleus accumbens

The current study aimed to explore how presynaptic dopamine (DA) function is altered following brief stress episodes and chronic ethanol self-administration and whether these neuroadaptations modify the acute effects of ethanol on DA dynamics. We used fast-scan cyclic voltammetry to evaluate changes in DA release and uptake parameters in rat nucleus accumbens brain slices by analyzing DA transients evoked through single pulse electrical stimulation. Adult male rats were divided into four groups: ethanol-naïve or ethanol drinking (six week intermittent two-bottle choice) and stressed (mild social defeat) or nonstressed. Results revealed that the mild stress significantly increased DA release and uptake in ethanol-naïve subjects, compared to nonstressed controls. Chronic ethanol self-administration increased the DA uptake rate and occluded the effects of stress on DA release dynamics. Bath-applied ethanol decreased stimulated DA efflux in a concentration-dependent manner in all groups; however, the magnitude of this effect was blunted by either stress or chronic ethanol, or by a combination of both procedures. Together, these findings suggest that stress and ethanol drinking may promote similar adaptive changes in accumbal presynaptic DA release measures and that these changes may contribute to the escalation in ethanol intake that occurs during the development of alcohol use disorder.

A role for BDNF/TrkB signaling in behavioral and physiological consequences of social defeat stress

Accumulating evidences underlie the importance of the interplay between environmental and genetic factors in contributing to the risk to develop mental illness. Brain-derived neurotrophic factor (BDNF) and its Tyrosine receptor kinase B (TrkB) receptor play a fundamental contribution to brain development and plastic adaptations to life events. In the present study, the potential for the BDNF/TrkB contribution in increasing vulnerability to negative social experiences was assessed by subjecting TrkB.T1 overexpressing mice to a chronic social defeat model. TrkB.T1 mice overexpress the dominant-negative truncated splice variant of TrkB receptor leading to decreased BDNF signaling. After repeated social defeat, mice were assessed in a longitudinal study for behavioral, physiological, endocrine and immune responses potentially related to psychiatric endophenotypes. TrkB.T1 overexpression corresponded to smaller changes in metabolic parameters such as body weight, food intake, feed efficiency and peripheral ghrelin levels compared with wild-type (wt) littermates following social defeat. Interestingly, 4 weeks after the last defeat, TrkB.T1 overexpressing mice exhibited more consistent social avoidance effects than what observed in wt subjects. Finally, previously unreported effects of TrkB mutations could be observed on lymphoid organ weight and on peripheral immune biomarker levels, such as interleukin-1α and regulated on activation, normal, T-cell expressed, and secreted (RANTES), thus suggesting a systemic role of BDNF signaling in immune function. In conclusion, the present data support a contribution of TrkB to stress vulnerability that, given the established role of TrkB in the response to antidepressant treatment, calls for further studies addressing the link between stress susceptibility and variability in drug efficacy.

Social defeat stress increases expression of mu-opioid receptor mRNA in rat ventral tegmental area.

Prompted by previous studies linking social defeat stress to changes in opioid antinociception, we evaluated the expression of mu-opioid receptor (MOR)-encoding mRNA in selected rat brain areas as a function of this type of stress. Because opioids mediate significant regulatory activities of brain dopamine neurons, dopaminergic loci in the ventral tegmental area (VTA) and substantia nigra (SN) were selected for analysis. Within 30 min after social defeat stress, the level of MOR-encoding mRNA, as detected and quantified by in situ hybridization histochemistry, increased in the lateral VTA and this increase was present for at least 6 h. In contrast, defeat stress was without effect on the expression of MOR-encoding mRNA in the SN. These data suggest that stress-induced alteration of MOR-encoding mRNA expression in the VTA may be involved in the consequences of social defeat stress.