Neurobiology of Sociability

  • Heather K. Caldwell
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 739)


Sociability consists of behaviors that bring animals together and those that keep animals apart. Remarkably, while the neural circuitry that regulates these two ”faces“ of sociability differ from one another, two neurohormones, oxytocin (Oxt) and vasopressin (Avp), have been consistently implicated in the regulation of both. In this chapter the the structure and function of the Oxt and Avp systems, the ways in which affiliative and aggressive behavior are studied and the roles of Oxt and Avp in the regulation of sociability will be briefly reviewed. Finally, work implicating Oxt and Avp in sociability in humans, with a focus on neuropsychiatric disorders will be highlighted.


Autism Spectrum Disorder Oxytocin Receptor Anterior Hypothalamus Prairie Vole Vasopressin Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Pinkham AE, Penn DL, Perkins DO et al. Implications for the neural basis of social cognition for the study of schizophrenia. Am J Psychiatry 2003; 160(5):815–824.PubMedCrossRefGoogle Scholar
  2. 2.
    Hill EL, Frith U. Understanding autism: insights from mind and brain. Philos Trans R Soc Lond B Biol Sci 2003; 358(1430):281–289.PubMedCrossRefGoogle Scholar
  3. 3.
    Hammock EA, Young LJ. Oxytocin, vasopressin and pair bonding: implications for autism. Philos Trans R Soc Lond B Biol Sci 2006; 361(1476):2187–2198.PubMedCrossRefGoogle Scholar
  4. 4.
    Lim MM, Young LJ. Neuropeptidergic regulation of affiliative behavior and social bonding in animals. Horm Behav 2006; 50(4):506–517.PubMedCrossRefGoogle Scholar
  5. 5.
    McCarthy MM, Wright CL, Schwarz JM. New tricks by an old dogma: mechanisms of the organizational/ activational hypothesis of steroid-mediated sexual differentiation of brain and behavior. Horm Behav 2009; 55(5):655–665.PubMedCrossRefGoogle Scholar
  6. 6.
    Berthold AA. Transplantation der Hoden. Arch Ant Physiol Wissenschr Med 1849:42–46.Google Scholar
  7. 7.
    Caldwell HK, Albers HE. Effect of photoperiod on vasopressin-induced aggression in Syrian hamsters. Horm Behav 2004; 46(4):444–449.PubMedCrossRefGoogle Scholar
  8. 8.
    Jasnow AM, Huhman KL, Bartness TJ et al. Short days and exogenous melatonin increase aggression of male Syrian hamsters (Mesocricetus auratus). Horm Behav 2002; 42:13–20.PubMedCrossRefGoogle Scholar
  9. 9.
    Elliott AS, Nunez AA. Photoperiod modulates the effects of steroids on sociosexual behaviors of hamsters. Physiol Behav 1992; 51:1189–1193.PubMedCrossRefGoogle Scholar
  10. 10.
    Demas GE, Polacek KM, Durazzo A et al. Adrenal hormones mediate melatonin-induced increases in aggression in male Siberian hamsters (Phodopus sungorus). Horm Behav 2004; 46(5):582–591.PubMedCrossRefGoogle Scholar
  11. 11.
    Jasnow AM, Huhman KL, Bartness TJ et al. Short-day increases in aggression are inversely related to circulating testosterone concentrations in male siberian hamsters (Phodopus sungorus). Horm Behav 2000; 38:102–110.PubMedCrossRefGoogle Scholar
  12. 12.
    Acher R, Chauvet J. The neurohypophysial endocrine regulatory cascade: precursors, mediators, receptors and effectors. Front Neuroendocrinol 1995; 16(3):237–289.PubMedCrossRefGoogle Scholar
  13. 13.
    Acher R, Chauvet J, Chauvet MT. Man and chimera: selective versus neutral oxytocin evolution. Adv Exp Med Biol 1995; 395:615–627.PubMedGoogle Scholar
  14. 14.
    Hara Y, Battey J, Gainer H. Structure of mouse vasopressin and oxytocin genes. Brain Res Mol Brain Res 1990; 8:319–324.PubMedCrossRefGoogle Scholar
  15. 15.
    Caldwell HK, Lee HJ, Macbeth AH et al. Vasopressin: behavioral roles of an “original” neuropeptide. Prog Neurobiol 2008; 84(1):1–24.PubMedCrossRefGoogle Scholar
  16. 16.
    Caldwell HK, Young WS 3rd, Lim R. Oxytocin and vasopressin: genetics and behavioral implications. In: Lajtha A, ed. Neuroactive Proteins and Peptides. 3rd Vol. New York: Springer, 2006:573–607.Google Scholar
  17. 17.
    Lee HJ, Macbeth AH, Pagani JH et al. Oxytocin: the great facilitator of life. Prog Neurobiol 2009; 88(2):127–151.PubMedGoogle Scholar
  18. 18.
    Adkins-Regan E. Neuroendocrinology of social behavior. ILAR J 2009; 50(1):5–14.PubMedGoogle Scholar
  19. 19.
    Neumann ID. Brain oxytocin: a key regulator of emotional and social behaviours in both females and males. J Neuroendocrinol 2008; 20(6):858–865.PubMedCrossRefGoogle Scholar
  20. 20.
    Veenema AH, Neumann ID. Central vasopressin and oxytocin release: regulation of complex social behaviours. Prog Brain Res 2008; 170:261–276.PubMedCrossRefGoogle Scholar
  21. 21.
    Carter CS, Grippo AJ, Pournajafi-Nazarloo H et al. Oxytocin, vasopressin and sociality. Prog Brain Res 2008; 170:331–336.PubMedCrossRefGoogle Scholar
  22. 22.
    Dale HH. On some physiological actions of ergot. J Physiol (Lond.) 1906; 34:163–206.Google Scholar
  23. 23.
    Ott I, Scott JC. The action of infundibulin upon the mammary secretion. Proc Soc Exp Biol Med 1910; 8:48–49.Google Scholar
  24. 24.
    Castel M, Morris JF. The neurophysin-containing innervation of the forebrain of the mouse. Neuroscience 1988; 24(3):937–966.PubMedCrossRefGoogle Scholar
  25. 25.
    Jirikowski GF, Caldwell JD, Stumpf WE et al. Topography of oxytocinergic estradiol target neurons in the mouse hypothalamus. Folia Histochem Cytobiol 1990; 28:3–9.PubMedGoogle Scholar
  26. 26.
    Wang Z, Zhou L, Hulihan TJ et al. Immunoreactivity of central vasopressin and oxytocin pathways in microtine rodents: a quantitative comparative study. J Comp Neurol 1996; 366(4):726–737.PubMedCrossRefGoogle Scholar
  27. 27.
    Ross HE, Cole CD, Smith Y et al. Characterization of the oxytocin system regulating affiliative behavior in female prairie voles. Neuroscience 2009; 162(4):892–903.PubMedCrossRefGoogle Scholar
  28. 28.
    Kimura T, Tanizawa O, Mori K et al. Structure and expression of a human oxytocin receptor. Nature 1992; 356:526–529.PubMedCrossRefGoogle Scholar
  29. 29.
    Kubota Y, Kimura T, Hashimoto K et al. Structure and expression of the mouse oxytocin receptor gene. Mol Cell Endocrinol 1996; 124(1–2):25–32.PubMedCrossRefGoogle Scholar
  30. 30.
    Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function and regulation. Physiol Rev 2001; 81(2):629–683.PubMedGoogle Scholar
  31. 31.
    Kremarik P, Freund-Mercier MJ, Stoeckel ME. Histoautoradiographic detection of oxytocin-and vasopressin-binding sites in the telencephalon of the rat. J Comp Neurol 1993; 333(3):343–359.PubMedCrossRefGoogle Scholar
  32. 32.
    Veinante P, Freund-Mercier MJ. Distribution of oxytocin-and vasopressin-binding sites in the rat extended amygdala: a histoautoradiographic study. J Comp Neurol 1997; 383(3):305–325.PubMedCrossRefGoogle Scholar
  33. 33.
    Insel TR, Gelhard R, Shapiro LE. The comparative distribution of forebrain receptors for neurohypophyseal peptides in monogamous and polygamous mice. Neuroscience 1991; 43(2–3):623–630.PubMedCrossRefGoogle Scholar
  34. 34.
    Sofroniew MV. Morphology of vasopressin and oxytocin neurones and their central and vascular projections. Prog Brain Res 1983; 60:101–114.PubMedCrossRefGoogle Scholar
  35. 35.
    Sofroniew MV. Vasopressin-and neurophysin-immunoreactive neurons in the septal region, medial amygdala and locus coeruleus in colchicine-treated rats. Neuroscience 1985; 15(2):347–358.PubMedCrossRefGoogle Scholar
  36. 36.
    Buijs RM, De Vries GJ, Van Leeuwen FW et al. Vasopressin and oxytocin: distribution and putative functions in the brain. Prog Brain Res 1983; 60:115–122.PubMedCrossRefGoogle Scholar
  37. 37.
    Buijs RM, Gash DM, Boer GJ. Vasopressin localization and putative functions in the brain. In: Vasopressin: Principles and Properties. New York: Plenum Press, 1987:91–115.Google Scholar
  38. 38.
    De Vries GJ, Buijs RM. The origin of the vasopressinergic and oxytocinergic innervation of the rat brain with special reference to the lateral septum. Brain Res 1983; 273(2):307–317.PubMedCrossRefGoogle Scholar
  39. 39.
    Sawchenko PE, Swanson LW. Immunohistochemical identification of neurons in the paraventricular nucleus of the hypothalamus that project to the medulla or to the spinal cord in the rat. J Comp Neurol 1982; 205(3):260–272.PubMedCrossRefGoogle Scholar
  40. 40.
    Ostrowski NL, Lolait SJ, Bradley DJ et al. Distribution of V1a and V2 vasopressin receptor messenger ribonucleic acids in rat liver, kidney, pituitary and brain. Endocrinology 1992; 131(1):533–535.PubMedCrossRefGoogle Scholar
  41. 41.
    Watters JJ, Poulin P, Dorsa DM. Steroid homone regulation of vasopressinergic neurotransmission in the central nervous system. Prog Brain Res 1998; 119:247–261.PubMedCrossRefGoogle Scholar
  42. 42.
    Johnson AE, Barberis C, Albers HE. Castration reduces vasopressin receptor binding in the hamster hypothalamus. Brain Res 1995; 674:153–158.PubMedCrossRefGoogle Scholar
  43. 43.
    Tribollet E, Barberis C, Arsenijevic Y. Distribution of vasopressin and oxytocin receptors in the rat spinal cord: sex-related differences and effect of castration in pudendal motor nuclei. Neuroscience 1997; 78(2):499–509.PubMedCrossRefGoogle Scholar
  44. 44.
    Ostrowski NL, Lolait SJ, Young WS. Cellular localization of vasopressin V1a receptor messenger ribonucleic acid in adult male rat brain, pineal and brain vasculature. Endocrinology 1994; 135(4): 1511–1528.PubMedCrossRefGoogle Scholar
  45. 45.
    Szot P, Bale TL, Dorsa DM. Distribution of messenger RNA for the vasopressin V1a receptor in the CNS of male and female rats. Brain Res Mol Brain Res 1994; 24(1–4):1–10.PubMedCrossRefGoogle Scholar
  46. 46.
    Antoni FA. Novel ligand specificity of pituitary vasopressin receptors in the rat. Neuroendocrinology 1984; 39:186–188.PubMedCrossRefGoogle Scholar
  47. 47.
    Lolait SJ, O’Carroll AM, Mahan LC et al. Extrapituitary expression of the rat V1b vasopressin receptor gene. Proc Natl Acad Sci USA 1995; 92(15):6783–6787.PubMedCrossRefGoogle Scholar
  48. 48.
    Saito M, Sugimoto T, Tahara A et al. Molecular cloning and characterization of rat V1b vasopressin receptor: evidence for its expression in extra-pituitary tissues. Biochem Biophys Res Commun 1995; 212:751–757.PubMedCrossRefGoogle Scholar
  49. 49.
    Vaccari C, Lolait SJ, Ostrowski NL. Comparative distribution of vasopressin V1b and oxytocin receptor messenger ribonucleic acids in brain. Endocrinology 1998; 139:5015–5033.PubMedCrossRefGoogle Scholar
  50. 50.
    Hernando F, Schoots O, Lolait SJ et al. Immunohistochemical localization of the vasopressin V1b receptor in the rat brain and pituitary gland: anatomical support for its involvement in the central effects of vasopressin. Endocrinology 2001; 142(4):1659–1668.PubMedCrossRefGoogle Scholar
  51. 51.
    Stemmelin J, Lukovic L, Salome N et al. Evidence that the lateral septum is involved in the antidepressantlike effects of the vasopressin V(1b) receptor antagonist SSR149415. Neuropsychopharmacology 2005; 30:35–42.PubMedCrossRefGoogle Scholar
  52. 52.
    Young WS, Li J, Wersinger SR et al. The vasopressin 1b receptor is prominent in the hippocampal area CA2 where it is unaffected by restraint stress or adrenalectomy. Neuroscience 2006; 143(4):1031–1039.PubMedCrossRefGoogle Scholar
  53. 53.
    Bankir L. Antidiuretic action of vasopressin: quantitative aspects and interaction between V1a and V2 receptor-mediated effects. Cardiovasc Res 2001; 51(3):372–390.PubMedCrossRefGoogle Scholar
  54. 54.
    Carter CS. Neuroendocrine perspectives on social attachment and love. Psychoneuroendocrinology 1998; 23(8):779–818.PubMedCrossRefGoogle Scholar
  55. 55.
    Uvnas-Moberg K. Physiological and endocrine effects of social contact. Ann N Y Acad Sci 1997; 807:146–163.PubMedCrossRefGoogle Scholar
  56. 56.
    Silk JB. The adaptive value of sociality in mammalian groups. Philos Trans R Soc Lond B Biol Sci 2007; 362(1480):539–559.PubMedCrossRefGoogle Scholar
  57. 57.
    Silk JB, Beehner JC, Bergman TJ et al. The benefits of social capital: close social bonds among female baboons enhance offspring survival. Proc Biol Sci 2009; 276(1670):3099–3104.PubMedCrossRefGoogle Scholar
  58. 58.
    Cameron EZ, Setsaas TH, Linklater WL. Social bonds between unrelated females increase reproductive success in feral horses. Proc Natl Acad Sci USA 2009; 106(33):13850–13853.PubMedCrossRefGoogle Scholar
  59. 59.
    Insel TR. A neurobiological basis of social attachment. Am J Psychiatry 1997; 154(6):726–735.PubMedGoogle Scholar
  60. 60.
    Young KA, Liu Y, Wang Z. The neurobiology of social attachment: a comparative approach to behavioral, neuroanatomical and neurochemical studies. Comp Biochem Physiol C Toxicol Pharmacol 2008; 148(4):401–410.PubMedCrossRefGoogle Scholar
  61. 61.
    Carter CS, Getz LL. Monogamy and the prairie vole. Sci Am 1993; 268(6):100–106.PubMedCrossRefGoogle Scholar
  62. 62.
    Carter CS, DeVries AC, Getz LL. Physiological substrates of mammalian monogamy: the prairie vole model. Neurosci Biobehav Rev 1995; 19(2):303–314.PubMedCrossRefGoogle Scholar
  63. 63.
    Williams JR, Catania KC, Carter CS. Development of partner preferences in female prairie voles (Microtus ochrogaster): the role of social and sexual experience. Horm Behav 1992; 26(3):339–349.PubMedCrossRefGoogle Scholar
  64. 64.
    Insel TR, Hulihan TA. A gender-specific mechanism for pair bonding: oxytocin and partner preference formation in monogamous voles. Behav Neurosci 1995; 109:782–789.PubMedCrossRefGoogle Scholar
  65. 65.
    Williams JR, Insel TR, Harbaugh CR et al. Oxytocin administered centrally facilitates formation of a partner preference in prairie voles (Microtus ochrogaster). J Neuroendocrinol 1994; 6:247–250.PubMedCrossRefGoogle Scholar
  66. 66.
    Insel TR, Shapiro LE. Oxytocin receptor distribution relects social organization in monogamous and polygamous voles. Proc Natl Acad Sci USA 1992; 89:5981–5985.PubMedCrossRefGoogle Scholar
  67. 67.
    Young LJ, Huot B, Nilsen R et al. Species differences in central oxytocin receptor gene expression: comparative analysis of promoter sequences. J Neuroendocrinol 1996; 8(10):777–783.PubMedCrossRefGoogle Scholar
  68. 68.
    Smeltzer MD, Curtis JT, Aragona BJ et al. Dopamine, oxytocin and vasopressin receptor binding in the medial prefrontal cortex of monogamous and promiscuous voles. Neurosci Lett 2006; 394(2):146–151.PubMedCrossRefGoogle Scholar
  69. 69.
    Insel TR, Winslow JT, Wang ZX et al. Oxytocin and the molecular basis of monogamy. Adv Exp Med Biol 1995; 395:227–234.PubMedGoogle Scholar
  70. 70.
    Cho MM, DeVries AC, Williams JR et al. The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). Behav Neurosci 1999; 113(1071):1079.Google Scholar
  71. 71.
    Liu Y, Wang ZX. Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles. Neuroscience 2003; 121:537–544.PubMedCrossRefGoogle Scholar
  72. 72.
    Young LJ, Lim MM, Gingrich B et al. Cellular mechanisms of social attachment. Horm Behav 2001; 40(2):133–138.PubMedCrossRefGoogle Scholar
  73. 73.
    Ross HE, Freeman SM, Spiegel LL et al. Variation in oxytocin receptor density in the nucleus accumbens has differential effects on affiliative behaviors in monogamous and polygamous voles. J Neurosci 2009; 29(5):1312–1318.PubMedCrossRefGoogle Scholar
  74. 74.
    Young LJ, Winslow JT, Nilsen R et al. Species differences in V1a receptor gene expression in monogamous and nonmonogamous voles: behavioral consequences. Behav Neurosci 1997; 111(3):599–605.PubMedCrossRefGoogle Scholar
  75. 75.
    Insel TR, Wang ZX, Ferris CF. Patterns of brain vasopressin receptor distribution associated with social organization in microtine rodents. J Neurosci 1994; 14:5381–5392.PubMedGoogle Scholar
  76. 76.
    Winslow JT, Hastings N, Carter CS et al. A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 1993; 365:545–548.PubMedCrossRefGoogle Scholar
  77. 77.
    Lim MM, Wang Z, Olazabal DE et al. Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 2004; 429(6993):754–757.PubMedCrossRefGoogle Scholar
  78. 78.
    Young LJ, Nilsen R, Waymire KG et al. Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole. Nature 1999; 400(6746):766–768.PubMedCrossRefGoogle Scholar
  79. 79.
    Lim MM, Hammock EA, Young LJ. The role of vasopressin in the genetic and neural regulation of monogamy. J Neuroendocrinol 2004; 16(4):325–332.PubMedCrossRefGoogle Scholar
  80. 80.
    Hammock EA, Young LJ. Functional microsatellite polymorphism associated with divergent social structure in vole species. Mol Biol Evol 2004; 21(6):1057–1063.PubMedCrossRefGoogle Scholar
  81. 81.
    Pitkow LJ, Sharer CA, Ren X et al. Facilitation of affiliation and pair-bond formation by vasopressin receptor gene transfer into the ventral forebrain of a monogamous vole. J Neurosci 2002; 21(18): 7392–7396.Google Scholar
  82. 82.
    Landgraf R, Frank E, Aldag JM et al. Viral vector-mediated gene transfer of the vole V1a vasopressin receptor in the rat septum: improved social discrimination and active social behaviour. Eur J Neurosci 2003; 18:403–411.PubMedCrossRefGoogle Scholar
  83. 83.
    Hammock EA, Young LJ. Microsatellite instability generates diversity in brain and sociobehavioral traits. Science 2005; 308(5728):1630–1634.PubMedCrossRefGoogle Scholar
  84. 84.
    Hammock EAD, Lim MM, Young LJ. Microsatellite polymorphism predicts vasopressin 1a receptor gene expression and behavior in prairie voles. Society for Neuroscience 2004:440–443.Google Scholar
  85. 85.
    Ophir AG, Wolff JO, Phelps SM. Variation in neural V1aR predicts sexual fidelity and space use among male prairie voles in semi-natural settings. Proc Natl Acad Sci USA 2008; 105(4):1249–1254.PubMedCrossRefGoogle Scholar
  86. 86.
    Ophir AG, Campbell P, Hanna K et al. Field tests of cis-regulatory variation at the prairie vole avpr1a locus: association with V1aR abundance but not sexual or social fidelity. Horm Behav 2008; 54(5):694–702.PubMedCrossRefGoogle Scholar
  87. 87.
    Numan M, Insel TR. The Neurobiology of Parental Care. New York: Springer-Verlag, 2003.Google Scholar
  88. 88.
    Svare BB. Maternal aggression in mammals. In: Gubernick DJ, Klopfer PH, eds. Parental Care in Mammals. New York: Plenum Press, 1981:179–210.CrossRefGoogle Scholar
  89. 89.
    Harmon AC, Huhman KL, Moore TO et al. Oxytocin inhibits aggression in female Syrian hamsters. J Neuroendocrinol 2002; 14(12):963–969.PubMedCrossRefGoogle Scholar
  90. 90.
    Ferris CF, Foote KB, Meltser HM et al. Oxytocin in the amygdala facilitates maternal aggression. Ann NY Acad Sci 1992; 652:456–457.PubMedCrossRefGoogle Scholar
  91. 91.
    Lubin DA, Elliott JC, Black MC et al. An oxytocin antagonist infused into the central nucleus of the amygdala increases maternal aggressive behavior. Behav Neurosci 2003; 117(2):195–201.PubMedCrossRefGoogle Scholar
  92. 92.
    Bales KL, Carter CS. Sex differences and developmental effects of oxytocin on aggression and social behavior in prairie voles (Microtus ochrogaster). Horm Behav 2003; 44(3):178–184.PubMedCrossRefGoogle Scholar
  93. 93.
    Giovenardi M, Padoin MJ, Cadore LP et al. Hypothalamic paraventricular nucleus modulates maternal aggression in rats: effects of ibotenic acid lesion and oxytocin antisense. Physiol Behav 1998; 63(3): 351–359.PubMedCrossRefGoogle Scholar
  94. 94.
    Consiglio AR, Lucion AB. Lesion of hypothalamic paraventricular nucleus and maternal aggressive behavior in female rats. Physiol Behav 1996; 59(4–5):591–596.PubMedCrossRefGoogle Scholar
  95. 95.
    Lee HJ, Caldwell HK, Macbeth AH et al. A conditional knockout mouse line of the oxytocin receptor. Endocrinology 2008; 149(7):3256–3263.PubMedCrossRefGoogle Scholar
  96. 96.
    Takayanagi Y, Yoshida M, Bielsky IF et al. Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proc Natl Acad Sci USA 2005; 102(44):16096–16101.PubMedCrossRefGoogle Scholar
  97. 97.
    Winslow JT, Hearn EF, Ferguson J et al. Infant vocalization, adult aggression and fear behavior in an oxytocin null mutant mouse. Horm Behav 2000; 37:145–155.PubMedCrossRefGoogle Scholar
  98. 98.
    DeVries AC, Young WS III, Nelson RJ. Reduced aggressive behaviour in mice with targeted disruption of the oxytocin gene. J Neuroendocrinol 1997; 9(5):363–368.PubMedCrossRefGoogle Scholar
  99. 99.
    Young WS, Shepard E, DeVries AC et al. Targeted reduction of oxytocin expression provides insights into its physiological roles. Adv Exp Med Biol 1998; 449:231–240PubMedCrossRefGoogle Scholar
  100. 100.
    Siegel HI. Aggressive behavior. In: The Hamster: Reproduction and Behavior. New York: Plenum Press, 1985:261–286.Google Scholar
  101. 101.
    Ferris CF, Albers HE, Wesolowski SM et al. Vasopressin injected into the hypothalamus triggers a complex stereotypic behavior in golden hamsters. Science 1984; 224:521–523.PubMedCrossRefGoogle Scholar
  102. 102.
    Ferris CF, Potegal M. Vasopressin receptor blockade in the anterior hypothalamus suppresses aggression in hamsters. Physiol Behav 1988; 44:235–239.PubMedCrossRefGoogle Scholar
  103. 103.
    Delville Y, Mansour KM, Ferris CF. Testosterone facilitates aggression by modulating vasopressin receptors in the hypothalamus. Physiol Behav 1996; 60(1):25–29.PubMedCrossRefGoogle Scholar
  104. 104.
    Blanchard RJ, Griebel G, Farrokhi C et al. AVP V(1b) selective antagonist SSR149415 blocks aggressive behaviors in hamsters. Pharmacol Biochem Behav 2005; 80(1):189–194.PubMedCrossRefGoogle Scholar
  105. 105.
    Albers HE, Huhman KL, Meisel RL et al. Hormonal basis of social conflict and communication. In: Hormones, Brain and Behavior. Amsterdam: Academic Press, 2002:393–433.CrossRefGoogle Scholar
  106. 106.
    Ferris CF, Melloni RH, Jr, Koppel G et al. Vasopressin/serotonin interactions in the anterior hypothalamus control aggressive behavior in golden hamsters. J Neurosci 1997; 17(11):4331–4340.PubMedGoogle Scholar
  107. 107.
    Grimes JM, Ricci LA, Melloni RH, Jr. Plasticity in anterior hypothalamic vasopressin correlates with aggression during anabolic-androgenic steroid withdrawal in hamsters. Behav Neurosci 2006; 120(1):115–124.PubMedCrossRefGoogle Scholar
  108. 108.
    Melloni RH, Jr, Conner DF, Hang PTX et al. Anabolic-androgenic steroid exposure during adolescence and aggressive behavior in golden hamsters. Physiol Behav 1997; 61:359–364.PubMedCrossRefGoogle Scholar
  109. 109.
    Harrison RJ, Connor DF, Nowak C et al. Chronic anabolic-androgenic steroid treatment during adolescence increases anterior hypothalamic vasopressin and aggression in intact hamsters. Psychoneuroendocrinology 2000; 25(4):317–338.PubMedCrossRefGoogle Scholar
  110. 110.
    Grimes JM, Ricci LA, Melloni RH, Jr. Alterations in anterior hypothalamic vasopressin, but not serotonin, correlate with the temporal onset of aggressive behavior during adolescent anabolic-androgenic steroid exposure in hamsters (Mesocricetus auratus). Behav Neurosci 2007; 121(5):941–948.PubMedCrossRefGoogle Scholar
  111. 111.
    Ferris CF, Meenan DM, Axelson JF et al. A vasopressin antagonist can reverse dominant/subordinate behavior in hamsters. Physiol Behav 1986; 38:135–138.PubMedCrossRefGoogle Scholar
  112. 112.
    Ferris CF, Axelson JF, Martin AM et al. Vasopressin immunoreactivity in the anterior hypothalamus is altered during the establishment of dominant/subordinate relationships between hamsters. Neuroscience 1989; 29(3):675–683.PubMedCrossRefGoogle Scholar
  113. 113.
    Cooper MA, Karom M, Huhman KL et al. Repeated agonistic encounters in hamsters modulate AVP V1a receptor binding. Horm Behav 2005; 48(5):545–551.PubMedCrossRefGoogle Scholar
  114. 114.
    Albers HE, Dean A, Karom MC et al. Role of V1a vasopressin receptors in the control of aggression in Syrian hamsters. Brain Res 2006; 1073–1074:425–430.PubMedCrossRefGoogle Scholar
  115. 115.
    De Vries GJ, Buijs RM, Swaab DF. The vasopressinergic innervation of the brain in normal and castrated rats. J Comp Neurol 1985; 233:236–254.CrossRefGoogle Scholar
  116. 116.
    De Vries GJ, Wang Z, Bullock NA 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. J Neurosci 1994; 14:1789–1794.PubMedGoogle Scholar
  117. 117.
    Van Leeuwen FW, Caffä SR, De Vries GJ. Vasopressin cells in the bed nucleus of the stria terminalis of the rat: sex differences and the influence of androgens. Brain Res 1985; 325:391–394.PubMedCrossRefGoogle Scholar
  118. 118.
    Desmedt A, Garcia R, Jaffard R. Vasopressin in the lateral septum promotes elemental conditioning to the detriment of contextual fear conditioning in mice. Eur J Neurosci 1999; 11:3913–3921.PubMedCrossRefGoogle Scholar
  119. 119.
    Everts HGJ, Koolhaas JM. Differential modulation of lateral septal vasopressin receptor blockade in spatial learning, social recognition and anxiety-related behaviors in rats. Behav Brain Res 1999; 99(1):7–16.PubMedCrossRefGoogle Scholar
  120. 120.
    Koolhaas JM, Moor E, Hiemstra Y et al. The testosterone-dependent vasopressinergic neurons in the medial amygdala and lateral septum: involvement in social behaviour in male rats. Proceedings of the Third International Vasopressin Conference. Paris/London: Colloque INSERM/John Libbey Eurotext Ltd., 1991:213–219.Google Scholar
  121. 121.
    Wang Z, Ferris CF, DeVries GJ. Role of septal vasopressin innervation in paternal behavior in prarie voles (Microtus ochrogaster). Proc Natl Acad Sci USA 1994; 91:400–404.PubMedCrossRefGoogle Scholar
  122. 122.
    Gobrogge KL, Liu Y, Young LJ et al. Anterior hypothalamic vasopressin regulates pair-bonding and drug-induced aggression in a monogamous rodent. Proc Natl Acad Sci USA 2009; 106(45):19144–19149.PubMedCrossRefGoogle Scholar
  123. 123.
    Compaan JC, Buijs RM, Pool CW et al. Differential lateral septal vasopressin innervation in aggressive and nonaggressive male mice. Brain Res Bull 1993; 30(1-2):1–6.PubMedCrossRefGoogle Scholar
  124. 124.
    Bester-Meredith JK, Young LJ, Marler CA. Species differences in paternal behavior and aggression in Peromyscus and their associations with vasopressin immunoreactivity and receptors. Horm Behav 1999; 36:25–38.PubMedCrossRefGoogle Scholar
  125. 125.
    Bester-Meredith JK, Marler CA. Vasopressin and aggression in cross-fostered California mice (Peromyscus californicus) and white-footed mice (Peromyscus leucopus). Horm Behav 2001; 40(1):51–64.PubMedCrossRefGoogle Scholar
  126. 126.
    Wersinger SR, Caldwell HK, Martinez L et al. Vasopressin 1a receptor knockout mice have a subtle olfactory deficit but normal aggression. Genes Brain Behav 2007; 6(6):540–551.PubMedCrossRefGoogle Scholar
  127. 127.
    Caldwell HK, Wersinger SR, Young WS 3rd. The role of the vasopressin 1b receptor in aggression and other social behaviours. Prog Brain Res 2008; 170:65–72.PubMedCrossRefGoogle Scholar
  128. 128.
    Wersinger SR, Caldwell HK, Christiansen M et al. Disruption of the vasopressin 1b receptor gene impairs the attack component of social behavior in mice. Genes Brain Behav 2006; 6(7):653–660.PubMedCrossRefGoogle Scholar
  129. 129.
    Wersinger SR, Ginns EI, O’Carroll AM et al. Vasopressin V1b receptor knockout reduces aggressive behavior in male mice. Mol Psychiatry 2002; 7(9):975–984.PubMedCrossRefGoogle Scholar
  130. 130.
    Caldwell HK, Young WS 3rd. Persistence of reduced aggression in vasopressin 1b receptor knockout mice on a more “wild” background. Physiol Behav 2009; 97(1):131–134.PubMedCrossRefGoogle Scholar
  131. 131.
    Hussain AA. Mechanism of nasal absorption of drugs. (0361-7742 (Print)).Google Scholar
  132. 132.
    Zak PJ, Kurzban R, Matzner WT. Oxytocin is associated with human trustworthiness. Horm Behav 2005; 48(5):522–527.PubMedCrossRefGoogle Scholar
  133. 133.
    Baumgartner T, Heinrichs M, Vonlanthen A et al. Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 2008; 58(4):639–650.PubMedCrossRefGoogle Scholar
  134. 134.
    Heinrichs M, von Dawans B, Domes G. Oxytocin, vasopressin and human social behavior. Front Neuroendocrinol 2009; 30(4):548–557.PubMedCrossRefGoogle Scholar
  135. 135.
    Rimmele U, Hediger K, Heinrichs M et al. Oxytocin makes a face in memory familiar. J Neurosci 2009; 29(1):38–42.PubMedCrossRefGoogle Scholar
  136. 136.
    Domes G, Heinrichs M, Michel A et al. Oxytocin improves “mind-reading” in humans. Biol Psychiatry 2007; 61(6):731–733.PubMedCrossRefGoogle Scholar
  137. 137.
    Guastella AJ, Carson DS, Dadds MR et al. Does oxytocin influence the early detection of angry and happy faces? Psychoneuroendocrinology 2009; 34(2):220–225.PubMedCrossRefGoogle Scholar
  138. 138.
    Guastella AJ, Mitchell PB, Dadds MR. Oxytocin increases gaze to the eye region of human faces. Biol Psychiatry 2008; 63(1):3–5.PubMedCrossRefGoogle Scholar
  139. 139.
    Thompson R, Gupta S, Miller K et al. The effects of vasopressin on human facial responses related to social communication. Psychoneuroendocrinology 2004; 29(1):35–48.PubMedCrossRefGoogle Scholar
  140. 140.
    Thompson RR, George K, Walton JC et al. Sex-specific influences of vasopressin on human social communication. Proc Natl Acad Sci USA 2006; 103(20):7889–7894.PubMedCrossRefGoogle Scholar
  141. 141.
    Matson JL, Nebel-Schwalm M. Assessing challenging behaviors in children with autism spectrum disorders: a review. Res Dev Disabil 2007; 28(6):567–579.PubMedCrossRefGoogle Scholar
  142. 142.
    Matson JL, Nebel-Schwalm MS. Comorbid psychopathology with autism spectrum disorder in children: an overview. Res Dev Disabil 2007; 28(4):341–352.PubMedCrossRefGoogle Scholar
  143. 143.
    Crawley JN, Chen T, Puri A et al. Social approach behaviors in oxytocin knockout mice: comparison of two independent lines tested in different laboratory environments. Neuropeptides 2007; 41(3):145–163.PubMedCrossRefGoogle Scholar
  144. 144.
    Lee HJ, Caldwell HK, Macbeth AH et al. Behavioural studies using temporal and spatial inactivation of the oxytocin receptor. Prog Brain Res 2008; 170:73–77.PubMedCrossRefGoogle Scholar
  145. 145.
    Macbeth AH, Lee HJ, Edds J et al. Oxytocin and the oxytocin receptor underlie intrastrain, but not interstrain, social recognition. Genes Brain Behav 2009; 8(5):558–567.PubMedCrossRefGoogle Scholar
  146. 146.
    Wersinger SR, Temple JL, Caldwell HK et al. Inactivation of the oxytocin and the vasopressin (Avp) 1b receptor genes, but not the Avp 1a receptor gene, differentially impairs the Bruce effect in laboratory mice (Mus musculus). Endocrinology 2008; 149(1):116–121.PubMedCrossRefGoogle Scholar
  147. 147.
    Winslow JT, Insel TR. The social deficits of the oxytocin knockout mouse. Neuropeptides 2002; 26(2–3):221–229.CrossRefGoogle Scholar
  148. 148.
    Ferguson JN, Aldag JM, Insel TR et al. Oxytocin in the medial amygdala is essential for social recognition in the mouse. J Neurosci 2001; 21(20):8278–8285.PubMedGoogle Scholar
  149. 149.
    Ferguson JN, Young LJ, Hearn EF et al. Social amnesia in mice lacking the oxytocin gene. Nat Genet 2000; 25:284–288.PubMedCrossRefGoogle Scholar
  150. 150.
    Modahl C, Green L, Fein D et al. Plasma oxytocin levels in autistic children. Biol Psychiatry 1998; 43(4):270–277.PubMedCrossRefGoogle Scholar
  151. 151.
    Green L, Fein D, Modahl C et al. Oxytocin and autistic disorder: alterations in peptide forms. Biol Psychiatry 2001; 50(8):609–613.PubMedCrossRefGoogle Scholar
  152. 152.
    Hollander E, Novotny S, Hanratty M et al. Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology 2003; 28(1):193–198.PubMedCrossRefGoogle Scholar
  153. 153.
    Hollander E, Bartz J, Chaplin W et al. Oxytocin increases retention of social cognition in autism. Biol Psychiatry 2007; 61(4):498–503.PubMedCrossRefGoogle Scholar
  154. 154.
    Wu S, Jia M, Ruan Y et al. Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol Psychiatry 2005; 58(1):74–77.PubMedCrossRefGoogle Scholar
  155. 155.
    Ylisaukko-oja T, Alarcon M, Cantor RM et al. Search for autism loci by combined analysis of Autism Genetic Resource Exchange and Finnish families. Ann Neurol 2006; 59(1):145–155.PubMedCrossRefGoogle Scholar
  156. 156.
    Jacob S, Brune CW, Carter CS et al. Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett 2007; 417(1):6–9.PubMedCrossRefGoogle Scholar
  157. 157.
    Wermter AK, Kamp-Becker I, Hesse P et al. Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level. Am J Med Genet B Neuropsychiatr Genet 2009.Google Scholar
  158. 158.
    Gregory SG, Connelly JJ, Towers AJ et al. Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med 2009; 7(1):62.PubMedCrossRefGoogle Scholar
  159. 159.
    Kim SJ, Young LJ, Gonen D et al. Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism. Mol Psychiatry 2002; 7(5):503–507.PubMedCrossRefGoogle Scholar
  160. 160.
    Wassink TH, Piven J, Vieland VJ et al. Examination of AVPR1a as an autism susceptibility gene. Mol Psychiatry 2004; 9(10):968–972.PubMedCrossRefGoogle Scholar
  161. 161.
    Yirmiya N, Rosenberg C, Levi S et al. Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills. Mol Psychiatry 2006; 11(5):488–494.PubMedCrossRefGoogle Scholar
  162. 162.
    Meyer-Lindenberg A, Kolachana B, Gold B et al. Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans. Mol Psychiatry 2009; 14(10):968–975.PubMedCrossRefGoogle Scholar
  163. 163.
    A merican Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed. Washington, DC: American Psychiatric Association; 2000.Google Scholar
  164. 164.
    Lee R, Ferris C, Van de Kar LD et al. Cerebrospinal fluid oxytocin, life history of aggression and personality disorder. Psychoneuroendocrinology 2009; 34(10):1567–1573.PubMedCrossRefGoogle Scholar
  165. 165.
    Coccaro EF, Kavoussi RJ, Hauger RL et al. Cerebrospinal fluid vasopressin levels: correlates with aggression and serotonin function in personality-disordered subjects. Arch Gen Psychiatry 1998; 55(8):708–714.PubMedCrossRefGoogle Scholar
  166. 166.
    Virkkunen M, Kallio E, Rawlings R et al. Personality profiles and state aggressiveness in Finnish alcoholic, violent offenders, fire setters and healthy volunteers. Arch Gen Psychiatry 1994; 51(1):28–33.PubMedCrossRefGoogle Scholar
  167. 167.
    Caldwell HK, Stephens SL, Young WS 3rd. Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice. Mol Psychiatry 2009; 14(2):190–196.PubMedCrossRefGoogle Scholar
  168. 168.
    Feifel D, Reza T. Oxytocin modulates psychotomimetic-induced deficits in sensorimotor gating. Psychopharmacology (Berl) 1999; 141(1):93–98.CrossRefGoogle Scholar
  169. 169.
    Lee PR, Brady DL, Shapiro RA et al. Social interaction deficits caused by chronic phencyclidine administration are reversed by oxytocin. Neuropsychopharmacology 2005; 30(10):1883–1894.PubMedCrossRefGoogle Scholar
  170. 170.
    Bujanow W. Letter: is oxytocin an anti-schizophrenic hormone? Can Psychiatr Assoc J 1974; 19(3):323.PubMedGoogle Scholar
  171. 171.
    Bujanow W. Hormones in the treatment of psychoses. Br Med J 1972; 4(5835):298.PubMedCrossRefGoogle Scholar
  172. 172.
    Beckmann H, Lang RE, Gattaz WF. Vasopressin—oxytocin in cerebrospinal fluid of schizophrenic patients and normal controls. Psychoneuroendocrinology 1985; 10(2):187–191.PubMedCrossRefGoogle Scholar
  173. 173.
    Glovinsky D, Kalogeras KT, Kirch DG et al. Cerebrospinal fluid oxytocin concentration in schizophrenic patients does not differ from control subjects and is not changed by neuroleptic medication. Schizophr Res 1994; 11(3):273–276.PubMedCrossRefGoogle Scholar
  174. 174.
    Goldman M, Marlow-O’Connor M, Torres I et al. Diminished plasma oxytocin in schizophrenic patients with neuroendocrine dysfunction and emotional deficits. Schizophr Res 2008; 98(1–3):247–255.CrossRefGoogle Scholar
  175. 175.
    Peskind ER, Raskind MA, Leake RD et al. Clonidine decreases plasma and cerebrospinal fluid arginine vasopressin but not oxytocin in humans. Neuroendocrinology 1987; 46(5):395–400.PubMedCrossRefGoogle Scholar
  176. 176.
    Raskind MA, Courtney N, Murburg MM et al. Antipsychotic drugs and plasma vasopressin in normals and acute schizophrenic patients. Biol Psychiatry 1987; 22(4):453–462.PubMedCrossRefGoogle Scholar
  177. 177.
    Feifel D, Priebe K. Vasopressin-deficient rats exhibit sensorimotor gating deficits that are reversed by subchronic haloperidol. Biol Psychiatry 2001; 50:425–433.PubMedCrossRefGoogle Scholar
  178. 178.
    Feifel D, Melendez G, Priebe K et al. The effects of chronic administration of established and putative antipsychotics on natural prepulse inhibition deficits in Brattleboro rats. Behav Brain Res 2007; 181(2):278–286.CrossRefGoogle Scholar
  179. 179.
    Feifel D, Melendez G, Shilling PD. Reversal of sensorimotor gating deficits in Brattleboro rats by acute administration of clozapine and a neurotensin agonist, but not haloperidol: a potential predictive model for novel antipsychotic effects. Neuropsychopharmacology 2004; 29(4):731–738.PubMedCrossRefGoogle Scholar
  180. 180.
    Feifel D, Mexal S, Melendez G et al. The brattleboro rat displays a natural deficit in social discrimination that is restored by clozapine and a neurotensin analog. Neuropsychopharmacology 2009; 34(8):2011–2018.PubMedCrossRefGoogle Scholar
  181. 181.
    Feifel D, Priebe K. The effects of cross-fostering on inherent sensorimotor gating deficits exhibited by Brattleboro rats. J Gen Psychol 2007; 134(2):173–182.PubMedCrossRefGoogle Scholar
  182. 182.
    Aragona BJ, Liu Y, Cameron A et al. Opposite modulation of social attachment by D1-and D2-type dopamine receptor activation in nucleus accumbens shell. Horm Behav 2003; 44:37.Google Scholar
  183. 183.
    Aragona BJ, Liu Y, Curtis JT et al. A critical role for nucleus accumbens dopamine in partner preference formation of male prairie voles (Microtus ochrogaster). J Neurosci 2003; 23:3483–3490.PubMedGoogle Scholar
  184. 184.
    Gingrich B, Liu Y, Cascio C et al. Dopamine D2 receptors in the nucleus accumbens are important for social attachment in female prairie voles (Microtus ochrogaster). Behav Neurosci 2000; 114(1):173–183.PubMedCrossRefGoogle Scholar
  185. 185.
    Aragona BJ, Liu Y, Yu YJ et al. Nucleus accumbens dopamine differentially mediates the formation and maintenance of monogamous pair bonds. Nat Neurosci 2006; 9(1):133–139.PubMedCrossRefGoogle Scholar
  186. 186.
    Northcutt KV, Lonstein JS. Social contact elicits immediate-early gene expression in dopaminergic cells of the male prairie vole extended olfactory amygdala. Neuroscience 2009; 163(1):9–22.PubMedCrossRefGoogle Scholar
  187. 187.
    Bosch OJ, Nair HP, Ahern TH et al. The CRF system mediates increased passive stress-coping behavior following the loss of a bonded partner in a monogamous rodent. Neuropsychopharmacology 2009; 34(6):1406–1415.PubMedCrossRefGoogle Scholar
  188. 188.
    Lim MM, Liu Y, Ryabinin AE et al. CRF receptors in the nucleus accumbens modulate partner preference in prairie voles. Horm Behav 2007; 51(4):508–515.PubMedCrossRefGoogle Scholar
  189. 189.
    Ring RH, Schechter LE, Leonard SK et al. Receptor and behavioral pharmacology of WAY-267464, a nonpeptide oxytocin receptor agonist. Neuropharmacology 2010; 58(1):69–77.PubMedCrossRefGoogle Scholar
  190. 190.
    Ring RH. The central vasopressinergic system: examining the opportunities for psychiatric drug development. Curr Pharm Des 2005; 11(2):205–225.PubMedCrossRefGoogle Scholar
  191. 191.
    Cirillo R, Gillio Tos E, Schwarz MK et al. Pharmacology of (2S,4Z)-N-[(2s)-2-hydroxy-2-phenylethyl]-4-(methoxyimino)-1-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxamide, a new potent and selective nonpeptide antagonist of the oxytocin receptor. J Pharmacol Exp Ther 2003; 306(1):253–261.PubMedCrossRefGoogle Scholar
  192. 192.
    Pitt GR, Batt AR, Haigh RM et al. Nonpeptide oxytocin agonists. Bioorg Med Chem Lett. 2004; 14(17):4585–4589.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Heather K. Caldwell
    • 1
  1. 1.Laboratory of Neuroendocrinology and Behavior; Department of Biological Sciences and School of Biomedical SciencesKent State UniversityUSA

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