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

Newman, Emily L.; Covington, Herbert E.; Suh, Junghyup; Bicakci, Matthew B; Ressler, Kerry J.; DeBold, Joseph F.; Miczek, Klaus A.

doi:10.1016/j.biopsych.2019.05.005

Cited by 130 publications

(101 citation statements)

References 106 publications

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“…Despite its effect on social avoidance, acute ketamine treatment (20 mg/kg, IP) failed to block the anhedonic effects of CSDS on intracranial self-stimulation (ICSS). [13][14][15][16] In a study by Kim et al 17 , its results suggest low-dose ketamine produces antidepressant effects and has independent behavioral and synaptic effects compared with higher doses of ketamine that are used to model schizophrenia. The above-mentioned study did not examine urinary bladder function.…”

Section: Discussionmentioning

confidence: 99%

Does ketamine ameliorate the social stress‐related bladder dysfunction in mice?

Yang

Chang

2020

Neurourology and Urodynamics

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Aims The aim of this study is to investigate whether ketamine could relieve the social stress (SS)‐related bladder dysfunction in mice. Materials and Methods The FVB mice were randomly assigned to either undergo SS exposure for 60 minutes per day on seven consecutive days for 4 weeks (SS1) or control without SS (SS0). The SS0 were then allocated to single or no injection of ketamine (SS0K1 and SS0K0). In the group of SS1, the SS1 mice were allocated to receive single injection of saline (SS1K0), single dose (SS1K1) or five daily dose of (SS1K5) ketamine injection (25 mg/kg/day/ip) since day 22. In vivo cystometry and tissue bath wire myography were performed on day 29. Serum and urine level of brain‐derived neurotrophic factor (BDNF) were measured with enzyme‐linked immunosorbent assay. Results In mice without social stress exposure, ketamine administration did not significantly affect voiding frequency (P > .05). SS1K0, SS1K1, and SS1K5 had significantly lower voiding frequency than that of control (SS1K0) (each n = 15, P < .05). Ketamine administration reversed the trend of decreased voiding frequency in SS1 mice. Stressed mice had significant higher serum level of BDNF that reduced by short‐term ketamine. Stressed mice had detrusor overactivity and impaired detrusor contractility which were not reversed by short‐term ketamine. Conclusions Social stress leads to elevated serum BDNF, infrequent voiding, detrusor overactivity, and impaired contractility. Short‐term administration of ketamine may improve SS‐related infrequent voiding and elevated serum BDNF level. However, ketamine did not improve SS‐related bladder dysfunction on urodynamic and myography studies.

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Section: Discussionmentioning

confidence: 99%

Does ketamine ameliorate the social stress‐related bladder dysfunction in mice?

Yang

Chang

2020

Neurourology and Urodynamics

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“…Several of these models have also been used to study the role of sex in these processes, either exposing animals to single repeated stressors, or to more complex protocols, which include combinations of multiple stressors like the unpredictable chronic mild stress and its variant, the chronic variable stress . Importantly, the classic paradigm of chronic social defeat stress, which has been widely used to study chronic stress exposure in male rodents, has recently been adapted for use in females of nonaggressive strains . To the best of our knowledge, however, molecular studies with this paradigm are still lacking.…”

Section: Chronic Stressmentioning

confidence: 99%

“…125,126 Importantly, the classic paradigm of chronic social defeat stress, which has been widely used to study chronic stress exposure in male rodents, has recently been adapted for use in females of nonaggressive strains. [127][128][129] To the best of our knowledge, however, molecular studies with this paradigm are still lacking. Overall, these protocols have very different designs and limitations: an important factor to consider when trying to compare results from different studies.…”

Section: Chronic Stressmentioning

confidence: 99%

Sex differences: Transcriptional signatures of stress exposure in male and female brains

Brivio

López

Chen

2020

Genes Brain and Behavior

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More than two‐thirds of patients suffering from stress‐related disorders are women but over two‐thirds of suicide completers are men. These are just some examples of the many sex differences in the prevalence and manifestations of stress‐related disorders, such as major depressive disorder, post‐traumatic stress disorder, and anxiety disorders, which have been extensively documented in clinical research. Nonetheless, the molecular origins of this sex dimorphism are still quite obscure. In response to this lack of knowledge, the NIH recently advocated implementing sex as biological variable in the design of preclinical studies across disciplines. As a result, a newly emerging field within psychiatry is trying to elucidate the molecular causes underlying the clinically described sex dimorphism. Several studies in rodents and humans have already identified many stress‐related genes that are regulated by acute and chronic stress in a sex‐specific fashion. Furthermore, current transcriptomic studies have shown that pathways and networks in male and female individuals are not equally affected by stress exposure. In this review, we give an overview of transcriptional studies designed to understand how sex influences stress‐specific transcriptomic changes in rodent models, as well as human psychiatric patients, highlighting the use of different methodological techniques. Understanding which mechanisms are more affected in males, and which in females, may lead to the identification of sex‐specific mechanisms, their selective contribution to stress susceptibility, and their role in the development of stress‐related psychiatric disorders.

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“…Due to the introduction of aggressive retired-breeder male mice in traditional RSDS, it cannot be used to induce psychological trauma similarly in female mice. There have been recent reports of modified female social defeat stress, 20,21 which-while potentially effective insofar as stress induction-vary significantly enough in approach, intensity, and duration to serve as serious confounding variables reducing internal validity.…”

Section: Discussionmentioning

confidence: 99%

Inflammation is a stronger predictor of psychological trauma exposure than behavior in repeated social defeat

et al. 2020

Preprint

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Word Count: 227 Total Word Count: 3,089Abstract Post-traumatic stress disorder (PTSD) is a psychiatric illness that results in an increased risk for a variety of inflammatory diseases. The exact etiology of this increased risk in unknown, and thus, several animal models have been developed to investigate the neuroimmune interactions of PTSD.Repeated social defeat stress (RSDS) is an established preclinical model of psychological trauma that recapitulates certain behavioral and inflammatory aspects of human PTSD. Furthermore, RSDS has been utilized to subgroup animals into susceptible and resilient populations based on one specific behavioral phenotype (i.e., social interaction). Herein, we conducted an extensive investigation of circulating inflammatory proteins after RSDS, and found significant elevations in various cytokines and chemokines after exposure to psychological trauma. When categorizing animals into either Highlights• Repeated social defeat stress (RSDS) reproducibly produces peripheral inflammation • Peripheral inflammation is not coupled to social interaction testing parameters • Susceptible and resilient categorization does not reflect peripheral inflammation • Anxiety-like behavioral parameters are linked to peripheral inflammation in RSDS • Peripheral inflammation is more predictive of trauma than behavior in RSDS

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

Cited by 130 publications

References 106 publications

Does ketamine ameliorate the social stress‐related bladder dysfunction in mice?

Does ketamine ameliorate the social stress‐related bladder dysfunction in mice?

Sex differences: Transcriptional signatures of stress exposure in male and female brains

Inflammation is a stronger predictor of psychological trauma exposure than behavior in repeated social defeat

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