Abstract
Rationale
Early-life stress (ELS) can increase anxiety, reduce prosocial behaviors, and impair brain regions that facilitate emotional and social development. This knowledge greatly stems from assessing disrupted mother–child relationships, while studies investigating the long-term effects of father-child relationships on behavioral development in children are scarce. However, available evidence suggests that fathers may uniquely influence a child’s behavioral development in a sex-specific manner. Rodent models examining mother–offspring interaction demonstrate relationships among ELS, neuroinflammatory mediators, and behavioral development; yet, the role paternal care may play in neuroimmune functioning remains unreported.
Objectives
Using the biparental California mouse (Peromyscus californicus), we examined to what extent paternal deprivation impairs social and anxiety-like behaviors, augments peripheral corticosterone (CORT) response, and alters central proinflammatory cytokine production following an acute stressor in adulthood.
Methods
Biparentally reared and paternally deprived (permanent removal of the sire 24 h post-birth) adult mice were assessed for sociability, preference for social novelty, social vigilance, and social avoidance behaviors, followed by novelty-suppressed feeding (NSF) testing for general anxiety-like behavior. Following an acute stressor, circulating CORT concentrations and region-specific proinflammatory cytokine concentrations were determined via radioimmunoassay and Luminex multianalyte analysis, respectively.
Results
In response to a novel same-sex conspecific, social vigilance behavior was associated with reduced sociability and increased avoidance in paternally deprived mice—an effect not observed in biparentally reared counterparts. Yet, in response to a familiar same-sex conspecific, social vigilance persisted but only in paternally deprived females. The latency to consume during NSF testing was not significantly altered by paternal deprivation. In response to an acute physical stressor, lower circulating CORT concentrations were observed in paternally deprived females. Compared to control-reared males, paternal deprivation increased hypothalamic interleukin-1β, but decreased hippocampal IL-6 protein concentration.
Conclusion
Greater social vigilance behavior was demonstrated in paternally deprived mice while they avoided social interaction with a novel same-sex conspecific; however, in response to a familiar same-sex conspecific, paternal deprivation increased social vigilance behavior but only in females. It is possible that different neurobiological mechanisms underlie these observed behavioral outcomes as sex-specific central proinflammatory cytokine and stress responsivity were observed in paternally deprived offspring.
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Data Availability
The authors are prepared to provide raw data from this publication, if ethically appropriate, to other investigators upon request.
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Acknowledgements
The authors thank Sabina Khantsis, Lidia Castillo, Priyanka Agarwal, Morgan Harris, Abigail Santoni, Hannah Lee, Alejandro E. Relling, Janet McCormick, and Lisa Hester for their behavioral and/or technical assistance and Zachary Weisenseel, Huazhen Chen, and Emily Oakley for feedback on data presentation.
Funding
This work was supported by the University of Maryland Department of Psychology and College of Behavioral and Social Sciences, The Ohio State University Department of Neuroscience and College of Medicine, and in part by a NIH grant to ERG (R01NS125589) and NIH-funded summer internship support for RB (R25NS120282).
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Walker, S.L., Sud, N., Beyene, R. et al. Paternal deprivation induces vigilance-avoidant behavior and accompanies sex-specific alterations in stress reactivity and central proinflammatory cytokine response in California mice (Peromyscus californicus). Psychopharmacology 240, 2317–2334 (2023). https://doi.org/10.1007/s00213-023-06354-2
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DOI: https://doi.org/10.1007/s00213-023-06354-2