title: Oxytocin promotes functional coupling between paraventricular nucleus and both sympathetic and parasympathetic cardioregulatory nuclei.
abstract: The neuropeptide oxytocin (OXT) facilitates prosocial behavior and selective sociality. In the context of stress, OXT also can down-regulate hypothalamic-pituitary-adrenal (HPA) axis activity, leading to consideration of OXT as a potential treatment for many socioaffective disorders. However, the mechanisms through which administration of exogenous OXT modulates social behavior in stressful environmental contexts are not fully understood. Here, we investigate the hypothesis that autonomic pathways are components of the mechanisms through which OXT aids the recruitment of social resources in stressful contexts that may elicit mobilized behavioral responses. Female prairie voles (Microtus ochrogaster) underwent a stressor (walking in shallow water) following pretreatment with intraperitoneal OXT (0.25mg/kg) or OXT antagonist (OXT-A, 20mg/kg), and were allowed to recover with or without their sibling cagemate. Administration of OXT resulted in elevated OXT concentrations in plasma, but did not dampen the HPA axis response to a stressor. However, OXT, but not OXT-A, pretreatment prevented the functional coupling, usually seen in the absence of OXT, between paraventricular nucleus (PVN) activity as measured by c-Fos immunoreactivity and HPA output (i.e. corticosterone release). Furthermore, OXT pretreatment resulted in functional coupling between PVN activity and brain regions regulating both sympathetic (i.e. rostral ventrolateral medulla) and parasympathetic (i.e. dorsal vagal complex and nucleus ambiguous) branches of the autonomic nervous system. These findings suggest that OXT increases central neural control of autonomic activity, rather than strictly dampening HPA axis activity, and provides a potential mechanism through which OXT may facilitate adaptive and context-dependent behavioral and physiological responses to stressors.
authors.affiliation: Northeastern University, United States; The Kinsey Institute at Indiana University, United States. Electronic address: jsn.r.yee@gmail.com.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Yee
authors.affiliation: Northeastern University, United States; The Kinsey Institute at Indiana University, United States.
authors.forename: William M
authors.initials: WM
authors.lastname: Kenkel
authors.affiliation: University of Amsterdam, Netherlands.
authors.forename: Jessie L
authors.initials: JL
authors.lastname: Frijling
authors.affiliation: Columbia University, United States.
authors.forename: Sonam
authors.initials: S
authors.lastname: Dodhia
authors.affiliation: The University of Chicago, United States.
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Onishi
authors.affiliation: University of Illinois at Chicago, United States.
authors.forename: Santiago
authors.initials: S
authors.lastname: Tovar
authors.affiliation: Case Western Reserve University, United States.
authors.forename: Maha J
authors.initials: MJ
authors.lastname: Saber
authors.affiliation: The University of North Carolina at Chapel Hill, United States.
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Lewis
authors.affiliation: Northwestern University, United States.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.affiliation: The Kinsey Institute at Indiana University, United States; The University of North Carolina at Chapel Hill, United States.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Porges
authors.affiliation: The Kinsey Institute at Indiana University, United States.
authors.forename: C Sue
authors.initials: CS
authors.lastname: Carter
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology*; D003411:Arvicolinae; D005260:Female; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D010121:Oxytocin / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D010121:Oxytocin
keywords: Brainstem; Oxytocin; Paraventricular nucleus; Prairie vole; Stress; c-Fos
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