The protective effects of social bonding on behavioral and pituitary-adrenal axis reactivity to chronic mild stress in prairie voles.

Positive social interactions may protect against stress. This study investigated the beneficial effects of pairing with a social partner on behaviors and neuroendocrine function in response to chronic mild stress (CMS) in 13 prairie vole pairs. Following 5 days of social bonding, male and female prairie voles were exposed to 10 days of CMS (mild, unpredictable stressors of varying durations, for instance, strobe light, white noise, and damp bedding), housed with either the social partner (paired group) or individually (isolated group). Active and passive behavioral responses to the forced swim test (FST) and tail-suspension test (TST), and plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone, were measured in all prairie voles following the CMS period. Both female and male prairie voles housed with a social partner displayed lower durations of passive behavioral responses (immobility, a maladaptive behavioral response) in the FST (mean ± SEM; females: 17.3 ± 5.4 s; males: 9.3 ± 4.6 s) and TST (females: 56.8 ± 16.4 s; males: 40.2 ± 11.3 s), versus both sexes housed individually (females, FST: 98.6 ± 12.9 s; females, TST: 155.1 ± 19.3 s; males, FST: 92.4 ± 14.1 s; males, TST: 158.9 ± 22.0 s). Female (but not male) prairie voles displayed attenuated plasma stress hormones when housed with a male partner (ACTH: 945 ± 24.7 pg/ml; corticosterone: 624 ± 139.5 ng/ml), versus females housed individually (ACTH: 1100 ± 23.2 pg/ml; corticosterone: 1064 ± 121.7 ng/ml). These results may inform understanding of the benefits of social interactions on stress resilience. Lay Summary: Social stress can lead to depression. The study of social bonding and stress using an animal model will inform understanding of the protective effects of social bonds. This study showed that social bonding in a rodent model can protect against behavioral responses to stress, and may also be protective against the elevation of stress hormones. This study provides evidence that bonding and social support are valuable for protecting against stress in humans

Social bonds, cardiovascular function, and serotonin : insights from an animal model

Advisors: Angela Grippo.Committee members: Michelle Lilly; Joe Magliano; Leslie Matuszewich; Jacob Peuler; Douglas Wallace.Social relationships positively influence psychological and biological function in humans and other mammals. The disruption of an individual's social environment through separation or death often results in social isolation, which can adversely impact mental and cardiovascular health (Frasure-Smith, Lesperance, & Talajic, 1993; Gore, 1978). The general purpose of this experiment is to further investigate neurobiological mechanisms mediating the adverse effects of social stress and focused on the role of serotonin in that relationship. An animal model was used to simulate social stress in humans. Specifically, the goal of this study is to explore the effects of sertraline hydrochloride (Zoloft) on the behavioral and physiological consequences of disrupted social bonds. We hypothesized that treatment with the antidepressant drug sertraline hydrochloride would buffer the deleterious changes in behavioral and cardiac function following social stress. Specifically, animals administered sertraline hydrochloride were expected to display lower heart rates and higher heart rate variability than the control group (i.e., vehicle only) during basal and behavioral assessment periods. To investigate this, male prairie voles were paired with an unrelated female partner for five days. Following this pairing period, all male prairie voles were isolated for the remainder of the study. After 5 days of isolation, half of the males received sertraline hydrochloride for the remaining 15 days of the experiment. Finally, behavioral assessments were conducted 24 hours apart on the final 2 days of the experiment. This investigation is the first to evaluate cardiac and behavioral responses to antidepressants in the context of social isolation using an animal model.;In general, sertraline hydrochloride was limited in its ability to buffer the negative cardiac and behavioral changes associated with social stress during this experiment. All male prairie voles (regardless of group assignment) displayed a significant increase in heart rate throughout isolation and a decrease in heart rate variability 10 days after isolation, which then recovered to pre-isolation levels. However, isolated male prairie voles administered sertraline hydrochloride did not display a statistically significant reduction in heart rate or increase in heart rate variability as predicted. Further, the sertraline hydrochloride group displayed increased heart rates on days 5 and 10, but not 14, of the drug administration period. The sertraline hydrochloride group's responses during the behavioral tests were mixed. During the tail-suspension test, the sertraline hydrochloride group displayed slightly, but not significantly, lower heart rates and higher heart rate variability than the vehicle group; however, during the forced swim test those results were reversed. Further, in the recovery period immediately following the tail-suspension test, the sertraline hydrochloride group exhibited a longer latency to return heart rate to basal levels, but subsequently displayed a slightly higher heart rate variability, versus the vehicle group.;In conclusion, sertraline hydrochloride treatment was not entirely effective in ameliorating social isolation induced increases in heart rate and depression-relevant behavior. The results of this experiment can help inform our understanding of the mechanisms through which social stress can negatively influence cardiac and behavioral function. Further, these findings contribute new knowledge regarding the utility of the prairie vole model for the study of potential neurobiological mechanisms that underlie the interactions between emotion and cardiovascular function, and how social bond disruption influences that relationship. Future work to extend the present results will improve our understanding of how negative social experiences mediate adverse behavioral and cardiovascular changes that consequently influence quality of life in humans.Ph.D. (Doctor of Philosophy

Social isolation and oxytocin antagonism increase emotion-related behaviors and heart rate in female prairie voles

Social isolation influences depression- and anxiety-related disorders and cardiac function. Oxytocin may mediate these conditions through interactions with social behavior, emotion, and cardiovascular function, via central and/or peripheral mechanisms. The present study investigated the influence of oxytocin antagonism using L-368,899, a selective oxytocin receptor antagonist that crosses the blood-brain barrier, on depression- and anxiety-related behaviors and heart rate in prairie voles. This rodent species has translational value for investigating interactions of social stress, behavior, cardiac responses, and oxytocin function. Adult female prairie voles were socially isolated or co-housed with a sibling for 4 weeks. A subset of animals in each housing condition was subjected to 4 sessions of acute L-368,899 (20 mg/kg, ip) or saline administration followed by a depression- or anxiety-related behavioral assessment. A subset of co-housed animals was evaluated for cardiac function following acute administration of L-368,899 (20 mg/kg, ip) and during behavioral assessments. Social isolation (vs. co-housing) increased depression- and anxiety-related behaviors. In isolated animals, L-368,899 (vs. vehicle) did not influence anxiety-related behaviors but exacerbated depression-related behaviors. In co-housed animals, L-368,899 exacerbated depression-related behaviors and increased heart rate at baseline and during behavioral tests. Social isolation produces emotion-related behaviors in prairie voles; central and/or peripheral oxytocin antagonism exacerbates these behavioral signs. Oxytocin antagonism induces depression-relevant behaviors and increases basal and stressor-reactive heart rate in co-housed prairie voles, similar to the consequences of social isolation demonstrated in this model. These results provide translational value for humans who experience behavioral and cardiac consequences of loneliness or social stress