Oxytocin, motherhood and bonding

Release of the peptide hormone oxytocin in the brain has been shown to influence both maternal, sexual and social bonding behaviours although there are a number of species differences. This review summarizes findings on the distributions of oxytocin and oxytocin receptors in the brain, together with factors governing their expression, release of the peptide in the brain and its behavioural actions. A model of how oxytocin may act to alter maternal and socio‐sexual behaviours is proposed which initially involves activation of oxytocin neurones in a single brain site, the paraventricular nucleus of the hypothalamus (PVN), following vaginal and cervical stimulation. This causes a co‐ordinated release of the peptide in the PVN and its terminal projection regions for up to 1 h and this promotes different behavioural components, primarily through modulation of classical transmitter systems.

[1]  D. Krehbiel,et al.  Naltrexone delays the onset of maternal behavior in primiparous parturient ewes , 1995, Pharmacology Biochemistry and Behavior.

[2]  P. Gustavsson,et al.  Oxytocin, prolactin, milk production and their relationship with personality traits in women after vaginal delivery or Cesarean section. , 1998, Journal of psychosomatic obstetrics and gynaecology.

[3]  T. Insel,et al.  Gene Targeting Approaches to Neuroendocrinology: Oxytocin, Maternal Behavior, and Affiliation , 1997, Hormones and Behavior.

[4]  T. Insel,et al.  Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. , 1992, Annals of the New York Academy of Sciences.

[5]  C. Fabre-nys,et al.  The Role of Oxytocin Release in the Mediobasal Hypothalamus of the Sheep in Relation to Female Sexual Receptivity , 1993, Journal of neuroendocrinology.

[6]  P. Emson,et al.  Somatostatin Potently Stimulates In Vivo Striatal Dopamine and γ‐Aminobutyric Acid Release by a Glutamate‐Dependent Action , 1998, Journal of neurochemistry.

[7]  C. Wotjak,et al.  Endogenous oxytocin is involved in short-term olfactory memory in female rats , 1998, Behavioural Brain Research.

[8]  E. Keverne,et al.  Oxytocin, amino acid and monoamine release in the region of the medial preoptic area and bed nucleus of the stria terminalis of the sheep during parturition and suckling , 1992, Brain Research.

[9]  K. Kendrick,et al.  The Role of Oxytocin Release in the Paraventricular Nucleus in the Control of Maternal Behaviour in the Sheep , 1996, Journal of neuroendocrinology.

[10]  A. Frantz,et al.  Brain β-Endorphin during Pregnancy, Parturition, and the Postpartum Period* , 1983 .

[11]  E. Keverne,et al.  Opioid receptor blockade reduces maternal affect and social grooming in rhesus monkeys , 1993, Psychoneuroendocrinology.

[12]  Intracerebral oxytocin is important for the onset of maternal behavior in inexperienced ewes delivered under peridural anesthesia. , 1992, Behavioral neuroscience.

[13]  P. Poindron,et al.  The importance of amniotic fluids for the establishment of maternal behaviour in experienced and inexperienced ewes , 1987, Animal Behaviour.

[14]  J. Russell,et al.  Oxytocin and vasopressin release within the supraoptic and paraventricular nuclei of pregnant, parturient and lactating rats: A microdialysis study , 1993, Neuroscience.

[15]  K. Kendrick,et al.  C‐fos and c‐jun in the paraventricular nucleus play a role in regulating peptide gene expression, oxytocin and glutamate release, and maternal behaviour , 1999, The European journal of neuroscience.

[16]  T. Insel,et al.  A gender-specific mechanism for pair bonding: oxytocin and partner preference formation in monogamous voles. , 1995, Behavioral neuroscience.

[17]  Q J Pittman,et al.  Septal and hippocampal release of vasopressin and oxytocin during late pregnancy and parturition in the rat. , 1991, Neuroendocrinology.

[18]  E. Keverne,et al.  Changes in the sensory processing of olfactory signals induced by birth in sheep. , 1992, Science.

[19]  K. Kendrick,et al.  Formation of olfactory memories mediated by nitric oxide , 1997, Nature.

[20]  T. Insel,et al.  Gonadal Steroids have Paradoxical Effects on Brain Oxytocin Receptors , 1993, Journal of neuroendocrinology.

[21]  E. Keverne,et al.  Effects of parturition and maternal experience on noradrenaline and acetylcholine release in the olfactory bulb of sheep. , 1993, Behavioral neuroscience.

[22]  A. Salm,et al.  Increases in Dendritic Bundling and Dye Coupling of Supraoptic Neurons after the Induction of Maternal Behavior a , 1992, Annals of the New York Academy of Sciences.

[23]  E. Keverne,et al.  Oxytocin and vasopressin release in the olfactory bulb of parturient ewes: changes with maternal experience and effects on acetylcholine, γ-aminobutyric acid, glutamate and noradrenaline release , 1995, Brain Research.

[24]  T. Insel,et al.  Are There Oxytocin Receptors in the Primate Brain? , 1997, Annals of the New York Academy of Sciences.

[25]  T R Insel,et al.  A gender-specific mechanism for pair bonding: oxytocin and partner preference formation in monogamous voles. , 1995, Behavioral neuroscience.

[26]  M. McCarthy.  Oxytocin inhibits infanticide in female house mice (Mus domesticus) , 1990, Hormones and Behavior.

[27]  D. Pfaff,et al.  Induction of FOS immunoreactivity in oxytocin neurons after sexual activity in female rats. , 1993, Neuroendocrinology.

[28]  T. Insel,et al.  Lesions of the hypothalamic paraventricular nucleus disrupt the initiation of maternal behavior , 1989, Physiology & Behavior.

[29]  Carol Carter Porges.  Neuroendocrine perspectives on social attachment and love , 1998 .

[30]  P. Whitten,et al.  Regulation of estrogen receptor beta mRNA in the brain: opposite effects of 17beta-estradiol and the phytoestrogen, coumestrol. , 1999, Brain research. Molecular brain research.

[31]  S. L. Parker,et al.  Stimulation of oxytocin release in the lactating rat by central excitatory amino acid mechanisms: evidence for specific involvement of R,S-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-sensitive glutamate receptors. , 1993, Endocrinology.

[32]  V. Hillegaart,et al.  Oxytocin as a possible mediator of SSRI-induced antidepressant effects , 1999, Psychopharmacology.

[33]  E. Keverne,et al.  Previous maternal experience potentiates the effect of parturition on oxytocin receptor mRNA expression in the paraventricular nucleus , 1999, The European journal of neuroscience.

[34]  C. Carter,et al.  NEUROENDOCRINE PERSPECTIVES ON SOCIAL ATTACHMENT AND LOVE , 1998, Psychoneuroendocrinology.

[35]  K. Kendrick,et al.  Olfactory memory and maternal behaviour-induced changes in c-fos and zif/268 mRNA expression in the sheep brain. , 1997, Brain research. Molecular brain research.

[36]  H. V. Tol,et al.  Regulation of the Rat Oxytocin Gene by Estradiol , 1990, Journal of neuroendocrinology.

[37]  P Richard,et al.  Release of oxytocin and vasopressin by magnocellular nuclei in vitro: specific facilitatory effect of oxytocin on its own release. , 1984, The Journal of endocrinology.

[38]  T. Insel,et al.  The ability of oxytocin to induce short latency maternal behavior is dependent on peripheral anosmia. , 1987, Behavioral neuroscience.

[39]  J. Burbach,et al.  A composite hormone response element mediates the transactivation of the rat oxytocin gene by different classes of nuclear hormone receptors. , 1993, Molecular endocrinology.

[40]  T. Insel,et al.  Oxytocin Receptor Distribution Reflects Social Organization in Monogamous and Polygamous Voles , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[41]  C. Breton,et al.  Gonadal steroid regulation of oxytocin and oxytocin receptor gene expression. , 1995, Advances in experimental medicine and biology.

[42]  S. Luckman.  Fos expression within regions of the preoptic area, hypothalamus and brainstem during pregnancy and parturition , 1995, Brain Research.

[43]  E. Keverne,et al.  Corticotrophin releasing factor mRNA expression in the sheep brain during pregnancy, parturition and lactation and following exogenous progesterone and oestrogen treatment. , 1995, Brain research. Molecular brain research.

[44]  D. Dluzen,et al.  Olfactory bulb norepinephrine depletion abolishes vasopressin and oxytocin preservation of social recognition responses in rats , 1998, Neuroscience Letters.

[45]  C. Pedersen,et al.  Oxytocin induces maternal behavior in virgin female rats. , 1982, Science.

[46]  B. A. Baldwin,et al.  Intracerebroventricular oxytocin stimulates maternal behaviour in the sheep. , 1987, Neuroendocrinology.

[47]  M. Tohyama,et al.  Localization of oxytocin receptor messenger ribonucleic acid in the rat brain. , 1993, Endocrinology.

[48]  E. Keverne,et al.  Effects of intracerebroventricular infusions of naltrexone and phentolamine on central and peripheral oxytocin release and on maternal behaviour induced by vaginocervical stimulation in the ewe , 1989, Brain Research.

[49]  D. Pfaff,et al.  Ovarian Steroid Modulation of Oxytocin Receptor Binding in the Ventromedial Hypothalamus , 1992, Annals of the New York Academy of Sciences.

[50]  K. Svensson,et al.  Mesotelencephalic dopamine system and reproductive behavior in the female rat: effects of ventral tegmental 6-hydroxydopamine lesions on maternal and sexual responsiveness. , 1991, Behavioral neuroscience.

[51]  E. Keverne,et al.  Intracranial dialysis measurement of oxytoxin, monoamine and uric acid release from the olfactory bulb and substantia nigra of sheep during parturition, suckling, separation from lambs and eating , 1988, Brain Research.

[52]  T. Insel,et al.  A neurobiological basis of social attachment. , 1997, The American journal of psychiatry.

[53]  T. Insel,et al.  The comparative distribution of forebrain receptors for neurohypophyseal peptides in monogamous and polygamous mice , 1991, Neuroscience.

[54]  M. Sofroniew.  Morphology of vasopressin and oxytocin neurones and their central and vascular projections. , 1983, Progress in brain research.

[55]  Thomas R. Insel,et al.  Oxytocin — A neuropeptide for affiliation: Evidence from behavioral, receptor autoradiographic, and comparative studies , 1992, Psychoneuroendocrinology.

[56]  T. Insel,et al.  Oxytocin, vasopressin, and autism: is there a connection? , 1999, Biological Psychiatry.

[57]  H. Kaba,et al.  The olfactory bulb: A critical site of action for oxytocin in the induction of maternal behaviour in the rat , 1996, Neuroscience.

[58]  C. Pedersen,et al.  Induction of maternal behavior in virgin rats after intracerebroventricular administration of oxytocin. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[59]  Diane M.Witt.  Oxytocin and rodent sociosexual responses: from behavior to gene expression , 1995, Neuroscience & Biobehavioral Reviews.

[60]  P. Richard,et al.  Excitatory effect of dopamine on oxytocin and vasopressin reflex releases in the rat , 1982, Brain Research.

[61]  Changes in Pro‐Opiomelanocortin and Pre‐proenkephalin mRNA Levels in the Ovine Brain during Pregnancy, Parturition and Lactation and in Response to Oestrogen and Progesterone , 1993, Journal of neuroendocrinology.

[62]  M. Mazurek,et al.  α 1-Adrenergic receptor activation releases vasopressin and oxytocin from perfused rat hypothalamic explants , 1986, Neuroscience Letters.

[63]  D. Witt.  Oxytocin and rodent sociosexual responses: from behavior to gene expression. , 1995, Neuroscience and biobehavioral reviews.

[64]  E. Tribollet,et al.  Autoradiographic detection of vasopressin binding sites, but not of oxytocin binding sites, in the sheep olfactory bulb , 1992, Brain Research.

[65]  O. Tanizawa,et al.  Oxytocin in the Cerebrospinal Fluid and Plasma of Pregnant and Nonpregnant Subjects , 1985, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[66]  T. Insel,et al.  Dopamine D2 receptor-mediated regulation of partner preferences in female prairie voles (Microtus ochrogaster): a mechanism for pair bonding? , 1999, Behavioral neuroscience.

[67]  T. Insel,et al.  Neuroendocrine bases of monogamy , 1998, Trends in Neurosciences.

[68]  M. Freund-Mercier,et al.  Oxytocin receptors on oxytocin neurones: histoautoradiographic detection in the lactating rat. , 1994, The Journal of physiology.

[69]  T. Insel,et al.  Oxytocin is required for nursing but is not essential for parturition or reproductive behavior. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[70]  R. Porter,et al.  Maternal recognition of neonates through olfactory cues , 1983, Physiology & Behavior.

[71]  E. Keverne,et al.  Regulation of maternal behavior and offspring growth by paternally expressed Peg3. , 1999, Science.

[72]  H. Albers,et al.  Role of oxytocin in the hypothalamic regulation of sexual receptivity in hamsters , 1995, Brain Research.

[73]  E. Keverne,et al.  Morphine and corticotrophin-releasing factor potentiate maternal acceptance in multiparous ewes after vaginocervical stimulation , 1991, Brain Research.

[74]  C. Carter,et al.  Physiological substrates of mammalian monogamy: The prairie vole model , 1995, Neuroscience & Biobehavioral Reviews.

[75]  E. Keverne,et al.  Influence of birth and maternal experience on olfactory bulb neurotransmitter release , 1993, Neuroscience.

[76]  E. Kerker,et al.  Inhibition of post-partum maternal behaviour in the rat by injecting an oxytocin antagonist into the cerebral ventricles. , 1987, The Journal of endocrinology.

[77]  E. Keverne,et al.  Changes in Oxytocin Immunoreactivity and mRNA Expression in the Sheep Brain during Pregnancy, Parturition and Lactation and in Response to Oestrogen and Progesterone , 1993, Journal of neuroendocrinology.

[78]  T. Insel,et al.  Increased accumulation of oxytocin messenger ribonucleic acid in the hypothalamus of the female rat: induction by long term estradiol and progesterone administration and subsequent progesterone withdrawal. , 1995, Endocrinology.

[79]  H. H. Swanson,et al.  Does oxytocin play a role in the onset of maternal behaviour in the rat? , 1984, The Journal of endocrinology.

[80]  A. Fleming,et al.  Vomeronasal and olfactory system modulation of maternal behavior in the rat. , 1979, Science.

[81]  S. L. Parker,et al.  Stimulation of oxytocin release in the lactating rat by a central interaction of alpha 1-adrenergic and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-sensitive excitatory amino acid mechanisms. , 1993, Endocrinology.

[82]  Michael E Greenberg,et al.  A Defect in Nurturing in Mice Lacking the Immediate Early Gene fosB , 1996, Cell.

[83]  F. Menniti,et al.  Intracerebroventricular administration of oxytocin and maternal behavior in rats after prolonged and acute steroid pretreatment , 1983, Hormones and Behavior.

[84]  E. Keverne,et al.  Microdialysis measurement of oxytocin, aspartate, γ-aminobutyric acid and glutamate release from the olfactory bulb of the sheep during vaginocervical stimulation , 1988, Brain Research.

[85]  E. Keverne,et al.  Cerebrospinal fluid levels of acetylcholinesterase, monoamines and oxytocin during labour, parturition, vaginocervical stimulation, lamb separation and suckling in sheep. , 1986, Neuroendocrinology.

[86]  M. F. Johnson,et al.  Oxytocin antiserum delays onset of ovarian steroid-induced maternal behavior , 1985, Neuropeptides.

[87]  E. Keverne,et al.  Neural Control of Maternal Behaviour and Olfactory Recognition of Offspring , 1997, Brain Research Bulletin.

[88]  C. Feinstein,et al.  Plasma oxytocin levels in autistic children , 1998, Biological Psychiatry.

[89]  D. Pfaff,et al.  Possible role for endogenous oxytocin in estrogen-facilitated maternal behavior in rats. , 1985, Neuroendocrinology.

[90]  G. Mason,et al.  Oxytocin activates the postpartum onset of rat maternal behavior in the ventral tegmental and medial preoptic areas. , 1994, Behavioral neuroscience.

[91]  R. L. Moss,et al.  Microelectrophoresis of cholinergic and aminergic drugs on paraventricular neurons. , 1972, The American journal of physiology.

[92]  K. Kendrick,et al.  Effect of substance P on acetylcholine and dopamine release in the rat striatum: a microdialysis study , 1993, Brain Research.

[93]  J. Russell,et al.  Hypothalamic opioid mechanisms controlling oxytocin neurones during parturition , 1988, Brain Research Bulletin.

[94]  G. Mason,et al.  Analysis of Oxytocin Release by Microdialysis and Interactions with Progesterone , 1992, Annals of the New York Academy of Sciences.

[95]  H. Kaba,et al.  The action of oxytocin originating in the hypothalamic paraventricular nucleus on mitral and granule cells in the rat main olfactory bulb , 1996, Neuroscience.

[96]  K. Houpt,et al.  Maternal behavior. , 1986, The Veterinary clinics of North America. Equine practice.