Advertisement

Hypothalamic Oxytocin Mediates Social Buffering of the Stress Response

  • Adam S. Smith
    Correspondence
    Address correspondence to Adam S. Smith, Ph.D., Florida State University, Department of Psychology and Program in Neuroscience, 1107 W Call Street, Psychology Department Building, Tallahassee, FL 32306
    Affiliations
    Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida
    Search for articles by this author
  • Zuoxin Wang
    Affiliations
    Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida
    Search for articles by this author

      Background

      While stressful life events can enhance the risk of mental disorders, positive social interactions can propagate good mental health and normal behavioral routines. Still, the neural systems that promote these benefits are undetermined. Oxytocin is a hormone involved in social behavior and stress; thus, we focus on the impact that social buffering has on the stress response and the governing effects of oxytocin.

      Methods

      Female prairie voles (Microtus ochrogaster) were exposed to 1 hour immobilization stress and then recovered alone or with their male partner to characterize the effect of social contact on the behavioral, physiological, and neuroendocrine stress response. In addition, we treated immobilized female voles recovering alone with oxytocin or vehicle and female voles recovering with their male partner with a selective oxytocin receptor antagonist or vehicle. Group sizes varied from 6 to 8 voles (N = 98 total).

      Results

      We found that 1 hour immobilization increased anxiety-like behaviors and circulating levels of corticosterone, a stress hormone, in female prairie voles recovering alone but not the female prairie voles recovering with their male partner. This social buffering by the male partner on biobehavioral responses to stress was accompanied by increased oxytocin release in the paraventricular nucleus of the hypothalamus. Intra-paraventricular nucleus oxytocin injections reduced behavioral and corticosterone responses to immobilization, whereas injections of an oxytocin receptor antagonist blocked the effects of the social buffering.

      Conclusions

      Together, our data demonstrate that paraventricular nucleus oxytocin mediates the social buffering effects on the stress response and thus may be a target for treatment of stress-related disorders.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Brown G.W.
        Life Events and Illness.
        Unwin Hyman, London1989
        • Dalgard O.S.
        • Dowrick C.
        • Lehtinen V.
        • Vazquez-Barquero J.L.
        • Casey P.
        • Wilkinson G.
        • et al.
        Negative life events, social support and gender difference in depression: A multinational community survey with data from the ODIN study.
        Soc Psychiatry Psychiatr Epidemiol. 2006; 41: 444-451
        • Cohen S.
        • Wills T.A.
        Stress, social support, and the buffering hypothesis.
        Psychol Bull. 1985; 98: 310-357
        • Smith A.S.
        • Wang Z.
        Salubrious effects of oxytocin on social stress-induced deficits.
        Horm Behav. 2012; 61: 320-330
        • Carter C.S.
        • Altemus M.
        Integrative functions of lactational hormones in social behavior and stress management.
        Ann N Y Acad Sci. 1997; 807: 164-174
        • Aragona B.J.
        • Wang Z.
        The prairie vole (Microtus ochrogaster): An animal model for behavioral neuroendocrine research on pair bonding.
        ILAR J. 2004; 45: 35-45
        • DeVries A.C.
        • Craft T.K.S.
        • Glasper E.R.
        • Neigh G.N.
        • Alexander J.K.
        2006 Curt P. Richter award winner: Social influences on stress responses and health.
        Psychoneuroendocrinology. 2007; 32: 587-603
        • Bosch O.J.
        • Nair H.P.
        • Ahern T.H.
        • Neumann I.D.
        • Young L.J.
        The CRF system mediates increased passive stress-coping behavior following the loss of a bonded partner in a monogamous rodent.
        Neuroendocrinology. 2009; 34: 1406-1415
        • DeVries A.C.
        • DeVries M.B.
        • Taymans S.E.
        • Carter C.S.
        Modulation of pair bonding in female prairie voles (Microtus ochrogaster) by corticosterone.
        Proc Natl Acad Sci U S A. 1995; 92: 7744-7748
        • DeVries A.C.
        • Taymans S.E.
        • Carter C.S.
        Social modulation of corticosteroid responses in male prairie voles.
        Ann N Y Acad Sci. 1997; 807: 494-497
        • Carter C.S.
        • DeVries A.C.
        • Taymans S.E.
        • Roberts R.L.
        • Williams J.R.
        • Chrousos G.P.
        Adrenocorticoid hormones and the development and expression of mammalian monogamy.
        Ann N Y Acad Sci. 1995; 771: 82-91
        • Neumann I.D.
        • Wigger A.
        • Torner L.
        • Holsboer F.
        • Landgraf R.
        Brain oxytocin inhibits basal and stress-induced activity of the hypothalamo-pituitary-adrenal axis in male and female rats: Partial action within the paraventricular nucleus.
        J Neuroendocrinol. 2000; 12: 235-243
        • Smith A.S.
        • Lieberwirth C.
        • Wang Z.
        Behavioral and physiological responses of female prairie voles to various stressful conditions.
        Stress. 2013; 16: 531-539
        • Grippo A.J.
        • Wu K.D.
        • Hassan I.
        • Carter C.S.
        Social isolation in prairie voles induces behaviors relevant to negative affect: Toward the development of a rodent model focused on co-occurring depression and anxiety.
        Depress Anxiety. 2008; 25: E17-E26
        • Lieberwirth C.
        • Liu Y.
        • Jia X.
        • Wang Z.
        Social isolation impairs adult neurogenesis in the limbic system and alters behaviors in female prairie voles.
        Horm Behav. 2012; 62: 357-366
        • Simsek Y.
        • Celik O.
        • Karaer A.
        • Yilmaz E.
        • Gul M.
        • Ozerol E.
        • et al.
        Elevated cardiac oxidative stress in newborn rats from mothers treated with atosiban.
        Arch Gynecol Obstet. 2012; 285: 655-661
        • Engelmann M.
        • Landgraf R.
        • Wotjak C.T.
        The hypothalamic-neurohypophysial system regulates the hypothalamic-pituitary-adrenal axis under stress: An old concept revisited.
        Front Neuroendocrinol. 2004; 25: 132-149
        • Evans J.J.
        • Forrest-Owen W.
        • McArdle C.A.
        Oxytocin receptor-mediated activation of phosphoinositidase C and elevation of cytosolic calcium in the gonadotrope-derived αT3-1 cell line.
        Endocrinology. 1997; 138: 2049-2055
        • Fukunaga Si Setoguchi S.
        • Hirasawa A.
        • Tsujimoto G.
        Monitoring ligand-mediated internalization of G protein-coupled receptor as a novel pharmacological approach.
        Life Sci. 2006; 80: 17-23
        • Gimpl G.
        • Fahrenholz F.
        The oxytocin receptor system: Structure, function, and regulation.
        Physiol Rev. 2001; 81: 630-668
        • Jezova D.
        • Skultetyova I.
        • Tokarev D.I.
        • Bakos P.
        • Vigas M.
        Vasopressin and oxytocin in stress.
        Ann N Y Acad Sci. 1995; 771: 192-203
      1. Neumann ID (2008): Brain oxytocin mediates beneficial consequences of close social interactions: From maternal love and sex. In: Pfaff D, Kordon C, Chanson P, Christen Y, editors. Hormones and Social Behaviour. Heidelberg, Germany: Springer-Verlag Berlin, 81–101.

        • Jezová D.
        • Michajlovskij N.
        • Kvetnanský R.
        • Makara G.B.
        Paraventricular and supraoptic nuclei of the hypothalamus are not equally important for oxytocin release during stress.
        Neuroendocrinology. 1993; 57: 776-781
        • Babygirija R.
        • Bulbul M.
        • Yoshimoto S.
        • Ludwig K.
        • Takahashi T.
        Central and peripheral release of oxytocin following chronic homotypic stress in rats.
        Auton Neurosci. 2012; 167: 56-60
        • Heinrichs M.
        • Baumgartner T.
        • Kirschbaum C.
        • Ehlert U.
        Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress.
        Biol Psychiatry. 2003; 54: 1389-1398
        • Neumann I.D.
        The advantage of social living: Brain neuropeptides mediate the beneficial consequences of sex and motherhood.
        Front Neuroendocrinol. 2009; 30: 483-496
        • Bartal IB-A Decety J.
        • Mason P.
        Empathy and pro-social behavior in rats.
        Science. 2011; 334: 1427-1430
        • Fraser O.N.
        • Stahl D.
        • Aureli F.
        Stress reduction through consolation in chimpanzees.
        Proc Natl Acad Sci U S A. 2008; 105: 8557-8562
        • Dunbar R.I.M.
        The social role of touch in humans and primates: Behavioural function and neurobiological mechanisms.
        Neurosci Biobehav Rev. 2010; 34: 260-268
        • Gordon I.
        • Martin C.
        • Feldman R.
        • Leckman J.F.
        Oxytocin and social motivation.
        Dev Cogn Neurosci. 2011; 1: 471-493
        • Waldherr M.
        • Neumann I.D.
        Centrally released oxytocin mediates mating-induced anxiolysis in male rats.
        Proc Natl Acad Sci U S A. 2007; 104: 16681-16684
        • Ross H.E.
        • Cole C.D.
        • Smith Y.
        • Neumann I.D.
        • Landgraf R.
        • Murphy A.Z.
        • Young L.J.
        Characterization of the oxytocin system regulating affiliative behavior in female prairie voles.
        Neuroscience. 2009; 162: 892-903
        • Kojima S.
        • Stewart R.A.
        • Demas G.E.
        • Alberts J.R.
        Maternal contact differentially modulates central and peripheral oxytocin in rat pups during a brief regime of mother-pup interaction that induces a filial huddling preference.
        J Neuroendocrinol. 2012; 24: 831-840
        • Bosch O.J.
        • Neumann I.D.
        Both oxytocin and vasopressin are mediators of maternal care and aggression in rodents: From central release to sites of action.
        Horm Behav. 2012; 61: 293-303
        • Pedersen C.A.
        • Boccia M.L.
        Oxytocin links mothering received, mothering bestowed and adult stress responses.
        Stress. 2002; 5: 259-267
        • Norman G.J.
        • Karelina K.
        • Morris J.S.
        • Zhang N.
        • Cochran M.
        • DeVries A.C.
        Social interaction prevents the development of depressive-like behavior post nerve injury in mice: A potential role for oxytocin.
        Psychosom Med. 2010; 72: 519-526
        • Bosch O.J.
        • Krömer S.A.
        • Brunton P.J.
        • Neumann I.D.
        Release of oxytocin in the hypothalamic paraventricular nucleus, but not central amygdala or lateral septum in lactating residents and virgin intruders during maternal defence.
        Neuroscience. 2004; 124: 439-448
        • Ebner K.
        • Bosch O.J.
        • Kromer S.A.
        • Singewald N.
        • Neumann I.D.
        Release of oxytocin in the rat central amygdala modulates stress-coping behaviour and the release of excitatory amino acids.
        Neuropsychopharmacology. 2004; 30: 223-230
        • Miller G.
        Neuroscience. The promise and perils of oxytocin.
        Science. 2013; 339: 267-269
        • Carter C.S.
        • Grippo A.J.
        • Pournajafi-Nazarloo H.
        • Ruscio M.G.
        • Porges S.W.
        Oxytocin, vasopressin and sociality.
        in: Neumann I.D. Landgraf R. Advances in Vasopressin and Oxytocin: From Genes to Behaviour to Disease. Elsevier, New York2008: 331-336
        • Holt-Lunstad J.
        • Birmingham W.A.
        • Light K.C.
        Influence of a “warm touch” support enhancement intervention among married couples on ambulatory blood pressure, oxytocin, alpha amylase, and cortisol.
        Psychosom Med. 2008; 70: 976-985
        • Gouin J.-P.
        • Carter C.S.
        • Pournajafi-Nazarloo H.
        • Glaser R.
        • Malarkey W.B.
        • Loving T.J.
        • et al.
        Marital behavior, oxytocin, vasopressin, and wound healing.
        Psychoneuroendocrinology. 2010; 35: 1082-1090
        • Ditzen B.
        • Schaer M.
        • Gabriel B.
        • Bodenmann G.
        • Ehlert U.
        • Heinrichs M.
        Intranasal oxytocin increases positive communication and reduces cortisol levels during couple conflict.
        Biol Psychiatry. 2009; 65: 728-731
        • Quirin M.
        • Kuhl J.
        • Düsing R.
        Oxytocin buffers cortisol responses to stress in individuals with impaired emotion regulation abilities.
        Psychoneuroendocrinology. 2011; 36: 898-904
        • Detillion C.E.
        • Craft T.K.S.
        • Glasper E.R.
        • Prendergast B.J.
        • DeVries A.C.
        Social facilitation of wound healing.
        Psychoneuroendocrinology. 2004; 29: 1004-1011
        • Ludwig M.
        • Leng G.
        Dendritic peptide release and peptide-dependent behaviours.
        Nat Rev Neurosci. 2006; 7: 126-136
        • Dabrowska J.
        • Hazra R.
        • Ahern T.H.
        • Guo J.-D.
        • McDonald A.J.
        • Mascagni F.
        • et al.
        Neuroanatomical evidence for reciprocal regulation of the corticotrophin-releasing factor and oxytocin systems in the hypothalamus and the bed nucleus of the stria terminalis of the rat: Implications for balancing stress and affect.
        Psychoneuroendocrinology. 2011; 36: 1312-1326
        • Windle R.J.
        • Kershaw Y.M.
        • Shanks N.
        • Wood S.A.
        • Lightman S.L.
        • Ingram C.D.
        Oxytocin attenuates stress-induced c-fos mRNA expression in specific forebrain regions associated with modulation of hypothalamo-pituitary-adrenal activity.
        J Neurosci. 2004; 24: 2974-2982
        • Blume A.
        • Bosch O.J.
        • Miklos S.
        • Luz T.
        • Wales L.
        • Waldherr M.
        • Neumann I.D.
        Oxytocin reduces anxiety via ERK1/2 activation: Local effect within the rat hypothalamic paraventricular nucleus.
        Eur J Neurosci. 2008; 27: 1947-1956
        • Paxinos G.
        • Watson C.
        The Rat Brain in Stereotaxic Coordinates.
        Academic, San Diego, CA1998

      Linked Article