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An Improved Model of Physical and Emotional Social Defeat: Different Effects on Social Behavior and Body Weight of Adolescent Mice by Interaction With Social Support.

ABSTRACT: Social stress is a prevalent etiological environmental factor that can affect health, especially during adolescence. Either experiencing or witnessing a traumatic event during adolescence can increase the risk of psychiatric disorders, such as PTSD. The present study attempted to establish an improved social stress model to better distinguish the effects of physical and emotional social stress on the behavior and physiology of adolescent mice. In addition, we investigated how social support affected these stress-induced changes in social behavior. On PND 28, male littermates were exposed to either physical stress (PS) or emotional stress (ES), afterwards, half of them were paired-housed and the others were singly housed. The PS exposed mice were directly confronted with a violent aggressor using the social defeat stress (SDS) paradigm for 15 min/trial (with the total of 10 trials randomly administered over a week), while the ES exposed mice were placed in a neighboring compartment to witness the PS procedure. Our results indicate that both stressors induced an effective stress response in adolescent mice, but PS and ES had differential influence in the context of relevant social anxiety/fear and social interaction with peers. Additionally, social support following stress exposure exerted beneficial effects on the social anxiety/fear in ES exposed mice, but not on PS exposed mice, suggesting that the type of stressor may affect the intervention efficacy of social support. These findings provide extensive evidence that physical and emotional stressors induce different effects. Moreover, ES exposed mice, rather than PS exposed mice, seemed to benefit from social support. In summary, the study suggests that this paradigm will be helpful in investigating the effects of psychological intervention for the treatment of stress-related psychiatric disorders.

SUBMITTER: Li M

PROVIDER: S-EPMC6297843 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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An Improved Model of Physical and Emotional Social Defeat: Different Effects on Social Behavior and Body Weight of Adolescent Mice by Interaction With Social Support.

Li Man M Xu Hang H Wang Weiwen W

Frontiers in psychiatry 20181211

Social stress is a prevalent etiological environmental factor that can affect health, especially during adolescence. Either experiencing or witnessing a traumatic event during adolescence can increase the risk of psychiatric disorders, such as PTSD. The present study attempted to establish an improved social stress model to better distinguish the effects of physical and emotional social stress on the behavior and physiology of adolescent mice. In addition, we investigated how social support affe ...[more]

PMID: 30618868

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Project description:Social support is a well-established predictor of improved physical health outcomes among adults. Establishing whether maternal social support may have an inter-generational positive impact on their child's physical health will provide important information for developing potential interventions and policies. Elevated body mass index (BMI) is one indicator of child health that is linked to increased risk for cardiovascular disease and other morbidities later in life. There is some evidence that maternal social support is associated with improved child and adolescent weight status; however, no studies have examined whether specific aspects of social support are more impactful than others or whether support availability is differentially impactful across developmental stages. The present study examined whether maternal perceptions of specific types of social support (i.e., financial support, non-monetary instrumental support, partner emotional support, and having a close supportive contact) were associated with lower adolescent BMI z-scores using longitudinal data collected over a 15-year period from the Future of Families and Child Wellbeing Study (n = 3146), which includes a high proportion of families experiencing socioeconomic disadvantage. Findings from linear regression models using specific types of social support measured across six waves of data collected over a 15-year period indicated that maternal perceptions of greater financial support were associated with lower adolescent BMI z-scores at 15 years (B = -0.05, 95% CI: -0.10, -0.004, P = 0.04), while the other types of support were not. Additional timing analyses demonstrated that perceived financial support during late childhood to adolescence was associated with lower adolescent BMI z-scores (B = -0.06, 95% CI: -0.11, -0.01, P = 0.01), whereas associations between support during infancy and early childhood were not detected. Study findings provide important insights for developing interventions and policies that improve maternal social supports to benefit child health.

Project description:Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g., reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction, and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of five social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct.

Project description:Sympathomimetics are effective, centrally acting drugs that induce weight loss through their potent anorexic and locomotor properties. We reported that sympathomimetics antagonize catecholamine-dependent, alpha-2 adrenergic receptor-dependent signal transduction mediated by chloride/bicarbonate transport. We posit that other drugs that target cellular chloride/bicarbonate antiport would similarly demonstrate anorectic properties, induce locomotion, and diminish weight gain. Male and female inbred mice were housed in groups or stressed by prolonged social isolation. Mice consumed either normal chow or a high fat, high fructose corn syrup, (i.e. "Western") diet. To inhibit chloride/bicarbonate transport, acetazolamide (ACT, 3 mM) was added to the drinking water. Rodents underwent evaluations of exploratory locomotion and learning with the object recognition test. Mice consuming a "Western" diet gain more weight compared to mice given a normal diet. When placed on a "Western" diet, stressed mice gained weight more rapidly than unstressed. The body weight of mice fed a normal diet with ACT was significantly reduced compared to control mice not given ACT (weight, g ± SEM), 23.7 ± 0.8 v. 21.0 ± 0.5, p = 0.02. ACT did not reduce weight gain in animals chronically maintained on a "Western" diet. Compared to unstressed mice, living in social isolation reduced spontaneous exploratory locomotion time, an indicator of anxiety, in male mice (sec +SEM) from 22.8 ± 3.5 to 12.2 ± 2.1 (p < 0.001), and in female mice, from 47 ± 5.7 to 19.6 ± 2.3 (p < 0.001). ACT had no effect on exploration time in unstressed mice, but ACT completely restored the diminished exploratory locomotion time found in stressed mice compared to unstressed mice. The ratio of time spent exploring new objects compared to familiar items (discrimination ratio [DR]) was reduced following social isolation in males from 2.6 ± 0.5 to 1.2 ± 0.2 (p < 0.05) and in females from 3.8 ± 0.6 to 1.5 ± 0.2 (p < 0.01). ACT normalized the DR ratio of the stressed mice. Decreased food consumption and greater locomotor activity induced by ACT may contribute to acute weight loss; this effect is diminished when rodents were maintained on an unhealthful Western diet. Inhibition of chloride/bicarbonate transport through agents such as acetazolamide could offer a safe, new approach to achieving weight loss.

Dataset Information

An Improved Model of Physical and Emotional Social Defeat: Different Effects on Social Behavior and Body Weight of Adolescent Mice by Interaction With Social Support.

Publications

An Improved Model of Physical and Emotional Social Defeat: Different Effects on Social Behavior and Body Weight of Adolescent Mice by Interaction With Social Support.

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