Mean Girls: Social Stress Models for Female Rodents

Kuske, Jace X.; Trainor, Brian C.

doi:10.1007/7854_2021_247

Cited by 17 publications

(4 citation statements)

References 163 publications

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“…Conversely, females that were exposed to witness defeat stress exhibited similar social self-administration of familiar social partners throughout the social stress exposure, and elevated social reward seeking and motivation after stress exposure, compared to control females. These data are reminiscent of previously reported witness defeat results in females that have found signs of heightened arousal, indicated by anxiogenic behavior, corticosterone levels in serum, proinflammatory markers, among others, which are suggested to describe a hypervigilance state 27, 54, 55 . Such hypervigilance has also been reported in females undergoing social defeat stress 56 .…”

Section: Discussionsupporting

confidence: 84%

Individual differences in volitional social motivation in male and female mice following social stress

Navarrete

Schneider

Smith

et al. 2022

Preprint

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Background: A key challenge in developing new treatments for neuropsychiatric illness is the disconnect between preclinical models and the complexity of human social behavior. We aimed to integrate voluntary social self-administration into a preclinical rodent stress model, as a platform for the identification of basic brain and behavior mechanisms underlying stress-induced individual differences in social motivation. Here, we introduce an operant social stress (OSS) procedure with male and female mice, where lever presses are reinforced by freely moving social interaction with a familiar social partner across social stress exposure. Methods: OSS is composed of three phases: (i) social self-administration training, (ii) social stress concurrent with daily reinforced social self-administration testing, and (iii) post-stress operant social reward testing under both non-reinforced and reinforced conditions. We resolve social stress-induced changes to social motivation behaviors using hierarchical clustering and aggregated z-scores, capturing the spectrum of individual differences that we describe with a social index score. Results: OSS captures a range of stress-related dynamic social motivation behaviors inclusive of sex as a biological variable. Both male and female mice lever press for access to a social partner, independent of social partner coat color or familiarity. Social stress attenuates social self-administration in males and promotes social reward seeking behavior in females. Hierarchical clustering does not adequately describe the relative distributions of social motivation following stress, which we find is better described as a non-binary behavioral distribution that we define by introducing the social index score. This index is stable across individual mice. Conclusion: We demonstrate that OSS can be used to detect stable individual differences in stress-induced changes to social motivation in male and female mice. These differences may reflect unique neurobiological, cellular and circuit mechanisms not captured by preclinical models that omit voluntary social behaviors. The inclusion of volitional social procedures may enhance the understanding of behavioral adaptations promoting stress resiliency and their mechanisms under more naturalistic conditions.

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Section: Discussionsupporting

confidence: 84%

Individual differences in volitional social motivation in male and female mice following social stress

Navarrete

Schneider

Smith

et al. 2022

Preprint

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“…Furthermore, the use of social defeat stress models, while informative, has been critiqued for its focus on physical aggression. This focus may overlook other forms of social stress, such as social isolation or hierarchical stress, which are also relevant to human addiction [98].…”

Section: Enhancing Ecological Validity Of Animal Modelsmentioning

confidence: 99%

Bridging Species and Disciplines: Incorporating Sociological Frameworks into Animal Models of Addiction

Fields

2024

Multidisciplinary Approach for Better Understanding of Addictive Behaviour [Working Title]

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This chapter explores the integration of sociological concepts and frameworks into animal models of addictive behaviors, aiming to enhance cross-species validity and deepen understanding of addiction’s multifaceted biopsychosocial roots. Through an interdisciplinary approach merging sociology and behavioral neuroscience, the investigation examines how experiences of discrimination and constrained agency may contribute to addiction vulnerability. Specifically, chronic social defeat stress’s impact on drug-seeking behaviors is explored, drawing parallels between rodent models and human experiences of racial battle fatigue resulting from daily racial microaggressions. The chapter also delves into how lack of autonomy, social isolation, and perceived loss of control due to discrimination may precipitate substance use as a coping mechanism. Additionally, the influence of social hierarchies, bonding patterns, and intergenerational epigenetic effects on resilience versus susceptibility to addiction is considered. Current methodologies are critically evaluated, with a proposal to enhance ecological validity in animal experiments to better simulate nuanced sociocultural stressors associated with addiction risk. Emphasizing the urgent need for cross-disciplinary collaborations between rodent researchers and social scientists, the chapter advocates for the incorporation of relevant sociological concepts into behavioral assays. Ultimately, the integration of diverse perspectives is crucial for comprehensively addressing the psychosocial and neurobiological dynamics underlying addiction across mammalian species and for developing more effective and equitable prevention and treatment approaches.

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“…Social defeat has been extensively used as one of the most representative animal model to study stress-induced social avoidance and the underlying neuronal mechanisms in different rodent species ( Toth et al, 2012 ; Toth and Neumann, 2013 ; Kuske and Trainor, 2022 ). Defeat involves repeated exposure to aggression from other conspecifics, resulting in psychological stress ( Kudryavtseva et al, 1991 ; Hollis and Kabbaj, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Limbic oxytocin receptor expression alters molecular signaling and social avoidance behavior in female prairie voles (Microtus ochrogaster)

Nerio-Morales,

Boender,

Young

et al. 2024

Front. Neurosci.

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IntroductionThe social defeat paradigm is the most representative animal model to study social anxiety disorder (SAD) and its underlying neuronal mechanisms. We have previously reported that defeat progressively reduces oxytocin receptors (OXTR) in limbic regions of the brain over an eight-week period in female prairie voles (Microtus ochrogaster). Oxytocin receptors activate the mitogen-activated protein kinase (MAPK) pathway, which has been previously associated with the anxiolytic effects of oxytocin. Here, we assessed the functional significance of OXTR in stress-induced social avoidance and the response of the MAPK signaling pathway in the nucleus accumbens (NAc), anterior cingulate cortex (ACC), and basolateral amygdala (BLA) of female prairie voles.MethodsIn experiment 1, Sexually naïve adult female prairie voles were defeated for three consecutive days and tested a week after for social preference/avoidance (SPA) test. Control subjects were similarly handled without defeat conditioning. In experiment 2, sexually and stress naïve adult female prairie voles were bilaterally injected into the NAc, ACC, or the BLA with a CRISPR/Cas9 virus targeting the Oxtr coding sequence to induce OXTR knockdown. Two weeks post-surgery, subjects were tested for SPA behavior. Viral control groups were similarly handled but injected with a control virus. A subgroup of animals from each condition in both experiments were similarly treated and euthanized without being tested for SPA behavior. Brains were harvested for OXTR autoradiography, western blot analysis of MAPK proteins and quantification of local oxytocin content in the NAc, BLA, ACC, and PVN through ELISA.ResultsSocial defeat reduced OXTR binding in the NAc and affected MAPK pathway activity and oxytocin availability. These results were region-specific and sensitive to exposure to the SPA test. Additionally, OXTR knockdown in the NAc, ACC, and BLA induced social avoidance and decreased basal MAPK activity in the NAc. Finally, we found that OXTR knockdown in these regions was associated with less availability of oxytocin in the PVN.ConclusionDysregulation of the oxytocin system and MAPK signaling pathway in the NAc, ACC, and BLA are important in social behavior disruptions in female voles. This dysregulation could, therefore, play an important role in the etiology of SAD in women.

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Mean Girls: Social Stress Models for Female Rodents

Cited by 17 publications

References 163 publications

Individual differences in volitional social motivation in male and female mice following social stress

Individual differences in volitional social motivation in male and female mice following social stress

Bridging Species and Disciplines: Incorporating Sociological Frameworks into Animal Models of Addiction

Limbic oxytocin receptor expression alters molecular signaling and social avoidance behavior in female prairie voles (Microtus ochrogaster)

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