Exogenous oxytocin administration alleviates anxiety- and depressive-like behaviors following permanent separation from offspring in paternal California mice (Peromyscus californicus)
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Date
2024-05
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The Ohio State University
Abstract
Introduction: Neuroplastic and endocrine-related alterations that accompany motherhood have been well-studied, with these changes promoting well-being in both the mother and child. While less is known about accompanying changes in fatherhood, rodent models suggest that first-time fathers experience alterations in endocrine state similar to that observed in first-time mothers (e.g., increased peripheral oxytocin [OXT] concentration, a hormone implicated in pair-bond formation and lactation). Additionally, available evidence suggests disrupting the bond between first-time fathers and offspring increases behavioral distress.
Methods: We utilized three groups of biparental California mice (Peromyscus californicus) to investigate the feasibility of alleviating behavioral consequences of permanent separation from offspring in first-time fathers: 1) control fathers: male mice who stayed with their offspring and mate from birth (PND 0) until weaning on PND 30 (N=10), 2) separated fathers treated with saline (SAL, N= 12), and 3) separated fathers treated with OXT (28.6mg/kg) (N=7). Separated fathers were single housed away from their mate and offspring on PND 1 and intraperitoneally [i.p.] injected with SAL or OXT every 72h until PND 30. On PND 30, behavioral tests (light/dark test [LDT], sucrose splash test [SST]) were performed, and tissues (plasma, brain, adrenal gland, spleen, thymus) were collected. An enzyme linked immunosorbent assay [ELISA] quantifying circulating corticosterone concentrations in plasma was performed on all mice as was real-time quantitative polymerase chain reaction [RT-qPCR] to assess relative hippocampal oxytocin receptor [OXTR] gene expression.
Results: Compared to SAL-treated father separated from their offspring, OXT treatment restored total grooming duration in fathers separated from their offspring to control levels during the SST (p = 0.034). Similar effects of OXT-treatment were observed in unsupported rearing behavior during the SST, such that fathers separated from their offspring exhibited restored frequency of unsupported rearing behavior to control levels (p = 0.0237). LDT behavior was not significantly altered by SAL or OXT treatment (p>0.05, for all comparisons). Additionally, terminal corticosterone concentrations and relative hippocampal OXTR gene expression were not different among groups (p>0.05).
Conclusions: Chronic treatment with OXT may alleviate anxiety-like (i.e., unsupported rearing behavior) and depressive-like (i.e., grooming duration) behaviors during the SST. The absence of group differences in the LDT aligns with previous literature which found no differences between control and stress conditions in the LDT within the California mouse species, suggesting this test may not serve as the best metric for anxiety-like behavior within this species. While separation from offspring is a stressor in many mammalian species, circulating corticosterone concentration did not differ among groups of fathers. Given that tissues were collected weeks after disruption of the father-offspring bond, the lack of an effect may suggest a compensatory adaptation to stress conditions like single housing and injections. Similarly, relative hippocampal OXTR gene expression did not differ among groups, which could also be due to adaptation to experimental conditions. While physiological correlates of stress and sociability did not differ among groups, the behavioral changes observed in OXT fathers demonstrate OXT’s importance in paternal experience in a rodent model that mimics human biparental care.
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Keywords
Biparental care, Paternal Experience, Oxytocin Administration, Offspring Separation