Sex and species differences in plasma oxytocin using an enzyme immunoassay

The neuropeptide hormone oxytocin (OT) is released peripherally and centrally and has been implicated in both physiology and behavior, especially sociosexual behaviors. Knowledge of OT levels in blood or other sources would be useful but these are rarely reported. Radioimmunoassay following extraction is the most commonly used method for measuring OT but is not ideal for use in small mammals in which blood volumes and concentrations of OT are low. Here we report a chemical and biological validation for a commercially available enzyme immunoassay for OT in unextracted plasma. In addition, comparisons of OT were made across species to allow comparison of the monoga- mous prairie vole (Microtus ochrogaster (Wagner, 1842)) to the polygynous Sprague Dawley rat. These species were chosen because OT plays a role in the formation of social bonds and we predicted that the highly social prairie vole would have higher plasma OT than the less social rat. Results of this comparison confirmed our hypothesis. Further, OT was significantly higher in females than in males in both species. Our results indicate that this enzyme immunoassay can be used to assay plasma OT in rodents and that the predicted correlations exist between plasma OT and gender as well as species-typical social behavior. Resume : L'hormone oxytocine (OT), un neuropeptide qui est libere tant en peripherie que dans le centre de l'organisme, est impliquee dans la physiologie et le comportement, particulierement les comportements sociosexuels. La connaissance des concentrations d'OT dans le sang et d'autres sources serait utile, mais elles sont rarement indiquees. Le dosage radioimmunologique apres extraction est la methode la plus communement utilisee pour la mesure d'OT, mais elle n'est pas ideale chez les petits mammiferes chez qui les volumes sanguins sont reduits et les concentrations d'OT faibles. Nous fournissons ici une validation chimique et biologique d'un essai immunoenzymatique disponible dans le commerce pour mesurer l'OT dans du plasma sans extraction. De plus, nous avons fait des comparaisons in- terspecifiques d'OT chez le campagnol des prairies (Microtus ochrogaster (Wagner, 1842)), une espece monogame, et le rat Sprague Dawley polygyne. Nous avons choisi ces especes parce qu'OT joue un role dans la formation des liens sociaux et nous avons predit que le campagnol des prairies qui est un animal tres sociable aurait des concentrations plasmatiques d'OT plus elevees que le rat qui l'est moins. Les resultats de la comparaison confirment notre hypothese. De plus, les concentrations d'OT sont significativement plus elevees chez les femelles que chez les mâles des deux es- peces. Nos resultats demontrent que l'essai immunoenzymatique peut servir a doser l'OT plasmatique chez les rongeurs et que les correlations predites existent bien entre les concentrations plasmatiques d'OT et le sexe, de meme qu'entre ces concentrations et les comportements sociaux particuliers a chaque espece.

[1]  T. Insel,et al.  Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole , 1999, Nature.

[2]  G. J. de Vries,et al.  Sex differences in the effects of testosterone and its metabolites on vasopressin messenger RNA levels in the bed nucleus of the stria terminalis of rats , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  M. Forsling,et al.  Variations in oxytocin secretion during the 4-day oestrous cycle of the rat. , 1993, The Journal of endocrinology.

[4]  T. Insel,et al.  Oxytocin Administered Centrally Facilitates Formation of a Partner Preference in Female Prairie Voles (Microtus ochrogaster) , 1994, Journal of neuroendocrinology.

[5]  T. Insel,et al.  Rearing Effects on Cerebrospinal Fluid Oxytocin Concentration and Social Buffering in Rhesus Monkeys , 2003, Neuropsychopharmacology.

[6]  M. Åstrand,et al.  Endocrine and behavioral traits in low-avoidance performing Sprague–Dawley rats , 1999, Regulatory Peptides.

[7]  H. Akil,et al.  Motivational Properties of Oxytocin in the Conditioned Place Preference Paradigm , 1997, Neuropsychopharmacology.

[8]  L. Young,et al.  The Effects of Peptides on Partner Preference Formation Are Predicted by Habitat in Prairie Voles , 2001, Hormones and Behavior.

[9]  C. Carter,et al.  The mating system of the prairie vole, Microtus ochrogaster: Field and laboratory evidence for pair-bonding , 1981, Behavioral Ecology and Sociobiology.

[10]  Allan E. Johnson.  The Regulation of Oxytocin Receptor Binding in the Ventromedial Hypothalamic Nucleus by Gonadal Steroids , 1992, Annals of the New York Academy of Sciences.

[11]  C. Carter,et al.  Male-related pheromones and the activation of female reproduction in the prairie vole (Microtus ochrogaster). , 1980, Biology of reproduction.

[12]  R. Zierer.  Impact of ether anesthesia on the hypophyseal content of oxytocin neurophysin I and II: a comparative study with ketamine in the rat. , 1991, Life sciences.

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

[14]  D. Dewsbury,et al.  The comparative psychology of monogamy. , 1987, Nebraska Symposium on Motivation. Nebraska Symposium on Motivation.

[15]  D. Ganten,et al.  Oxytocin unlike vasopressin is a stress hormone in the rat. , 1983, Neuroendocrinology.

[16]  D. Monaghan,et al.  Dextromethorphan and Other N-Methyl-D-Aspartate Receptor Antagonists Are Teratogenic in the Avian Embryo Model , 1998, Pediatric Research.

[17]  Gregory F Ball,et al.  Time course of the estradiol-dependent induction of oxytocin receptor binding in the ventromedial hypothalamic nucleus of the rat. , 1989, Endocrinology.

[18]  A. Sohlström,et al.  Postnatal Oxytocin Injections Cause Sustained Weight Gain and Increased Nociceptive Thresholds in Male and Female Rats , 1998, Pediatric Research.

[19]  C. Carter,et al.  Sex differences and developmental effects of oxytocin on aggression and social behavior in prairie voles (Microtus ochrogaster) , 2003, Hormones and Behavior.

[20]  T. Insel,et al.  Hypothalamic Vasopressin Gene Expression Increases in Both Males and Females Postpartum in a Biparental Rodent , 2000, Journal of neuroendocrinology.

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

[22]  Thomas R. Insel,et al.  Enhanced social interactions in rats following chronic, centrally infused oxytocin , 1992, Pharmacology Biochemistry and Behavior.

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

[24]  Cushing,et al.  Prior Exposure To Oxytocin Mimics the Effects Of Social Contact and Facilitates Sexual Behaviour In Females , 1999, Journal of neuroendocrinology.

[25]  C. Carter,et al.  Hormonal correlates of sexual behavior and ovulation in male-induced and postpartum estrus in female prairie voles , 1989, Physiology & Behavior.

[26]  E. Shirtcliff,et al.  Use of salivary biomarkers in biobehavioral research: cotton-based sample collection methods can interfere with salivary immunoassay results , 2001, Psychoneuroendocrinology.

[27]  C. Johansson,et al.  Endocrine and behavioral traits in low-avoidance Sprague-Dawley rats. , 1999, Regulatory peptides.

[28]  J. Russell,et al.  The maternal brain : neurobiological and neuroendocrine adaptation and disorders in pregnancy and post partum , 2001 .

[29]  D. Kleiman,et al.  Monogamy in Mammals , 1977, The Quarterly Review of Biology.

[30]  T. Insel,et al.  Oxytocin, vasopressin, and the neuroendocrine basis of pair bond formation. , 1998, Advances in experimental medicine and biology.

[31]  C. Wotjak,et al.  Behavioral Consequences of Intracerebral Vasopressin and Oxytocin: Focus on Learning and Memory * * This paper is dedicated to our friend and scientific teacher Prof. Dr Armin Ermisch (1935–1995). , 1996, Neuroscience & Biobehavioral Reviews.

[32]  J. Winslow,et al.  Social status in pairs of male squirrel monkeys determines the behavioral response to central oxytocin administration , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  D. Schams,et al.  Development of a sensitive enzymeimmunoassay for oxytocin determination in bovine plasma. , 1998, Animal reproduction science.

[34]  C. Pedersen,et al.  Oxytocin Control of Maternal Behavior Regulation by Sex Steroids and Offspring Stimuli a , 1997, Annals of the New York Academy of Sciences.

[35]  C. Wotjak,et al.  Emotional Stress Triggers Intrahypothalamic But Not Peripheral Release of Oxytocin in Male Rats , 1999, Journal of neuroendocrinology.

[36]  B. Penke,et al.  Specific radioimmunoassay of oxytocin in rat plasma. , 1994, Endocrine regulations.

[37]  R. Landgraf.  Simultaneous measurement of arginine vasopressin and oxytocin in plasma and neurohypophyses by radioimmunoassay. , 1981, Endokrinologie.

[38]  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.

[39]  D. Blanchard,et al.  Sexual and aggressive interactions in a visible burrow system with provisioned burrows , 2001, Physiology & Behavior.

[40]  C. Pedersen,et al.  Estradiol influences oxytocin-immunoreactive brain systems , 1988, Neuroscience.

[41]  G. J. Vries,et al.  Brain Sexual Dimorphism and Sex Differences in Parental and Other Social Behaviors a , 1997, Annals of the New York Academy of Sciences.

[42]  S. Challinor,et al.  Pattern of oxytocin concentrations in the plasma and cerebrospinal fluid of lactating rhesus monkeys (Macaca mulatta): evidence for functionally independent oxytocinergic pathways in primates. , 1990, The Journal of clinical endocrinology and metabolism.

[43]  C. Carter,et al.  Oxytocin Receptor Binding in Female Prairie Voles: Endogenous and Exogenous Oestradiol Stimulation , 1991, Journal of neuroendocrinology.

[44]  C. Pedersen,et al.  Oxytocin facilitates the sexual receptivity of estrogen-treated female rats , 1986, Neuropeptides.

[45]  C. Carter,et al.  Central and peripheral effects of oxytocin administration in prairie voles (Microtus ochrogaster) , 1990, Pharmacology Biochemistry and Behavior.

[46]  J. Legros,et al.  Simultaneous radioimmunoassay for plasma arginine-vasopressin and oxytocin using DEAE Sephadex A 25 extraction , 1984, Journal of endocrinological investigation.

[47]  E. Birney,et al.  Parental care and mating system of the prairie vole, Microtus ochrogaster , 1979, Behavioral Ecology and Sociobiology.

[48]  S. Seif,et al.  Oxytocin in human plasma: correlation with neurophysin and stimulation with estrogen. , 1981, The Journal of clinical endocrinology and metabolism.

[49]  V. Geenen,et al.  Novel plasma extraction procedure and development of a specific enzyme-immunoassay of oxytocin: application to clinical and biological investigations of small cell carcinoma of the lung. , 2001, Scandinavian journal of clinical and laboratory investigation.

[50]  P. Sharp,et al.  An analysis of physiological mechanisms underlying the antigonadotropic action of intracranial prolactin in ring doves. , 1999, General and comparative endocrinology.

[51]  C. Carter,et al.  The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). , 1999, Behavioral neuroscience.

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

[53]  T. Insel,et al.  Oxytocin in the Medial Amygdala is Essential for Social Recognition in the Mouse , 2001, The Journal of Neuroscience.

[54]  K. Terao,et al.  Simple method for assaying serum oxytocin and changes of serum oxytocin level during parturition in cynomolgus monkeys. , 2002, Experimental animals.

[55]  T. Insel,et al.  The neurobiology of attachment , 2001, Nature Reviews Neuroscience.

[56]  C.,et al.  Physiological Substrates of Mammalian Monogamy : The Prairie Vole Model , 2002 .

[57]  Robert Kurzban,et al.  The neurobiology of trust. , 2008, Annals of the New York Academy of Sciences.

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