, Volume 229, Issue 4, pp 639–651 | Cite as

Antiaggressive activity of central oxytocin in male rats

  • Federica Calcagnoli
  • Sietse F. de Boer
  • Monika Althaus
  • Johan A. den Boer
  • Jaap M. Koolhaas
Original Investigation



A substantial body of research suggests that the neuropeptide oxytocin promotes social affiliative behaviors in a wide range of animals including humans. However, its antiaggressive action has not been unequivocally demonstrated in male laboratory rodents.


Our primary goal was to examine the putative serenic effect of oxytocin in a feral strain (wild type Groningen, WTG) of rats that generally show a much broader variation and higher levels of intermale aggression than commonly used laboratory strains of rats.


Resident animals were intracerebroventricularly (icv) administered with different doses of synthetic oxytocin and oxytocin receptor antagonist, alone and in combination, in order to manipulate brain oxytocin functioning and to assess their behavioral response to an intruder.


Our data clearly demonstrate that acute icv administered oxytocin produces dose-dependent and receptor-selective changes in social behavior, reducing aggression and potentiating social exploration. These antiaggressive effects are stronger in the more offensive rats. On the other hand, administration of an oxytocin receptor antagonist tends to increase (nonsignificantly) aggression only in low–medium aggressive animals.


These results suggest that transiently enhancing brain oxytocin function has potent antiaggressive effects, whereas its attenuation tends to enhance aggressiveness. In addition, a possible inverse relationship between trait aggression and endogenous oxytocinergic signaling is revealed. Overall, this study emphasizes the importance of brain oxytocinergic signaling for regulating intermale offensive aggression. This study supports the suggestion that oxytocin receptor agonists could clinically be useful for curbing heightened aggression seen in a range of neuropsychiatric disorders like antisocial personality disorder, autism, and addiction.


Oxytocin Offensive aggression Social exploration Individual variability 



We would like to thank Dr. M. Manning (University of Toledo, OH, USA) for kindly providing the oxytocin receptor antagonistpeptidergic compound.


  1. Altemus M, Pigott T, Kalogeras KT, Demitrack M, Dubbert B, Murphy DL, Gold PW (1992) Abnormalities in the regulation of vasopressin and corticotropin releasing factor secretion in obsessive–compulsive disorder. Arch Gen Psychiatry 49(1):9–20PubMedCrossRefGoogle Scholar
  2. Bales KL, Carter CS (2003) Sex differences and developmental effects of oxytocin on aggression and social behavior in prairie voles (Microtus ochrogaster). Horm Behav 44(3):178–184PubMedCrossRefGoogle Scholar
  3. Barraza JA, Zak PJ (2009) Empathy toward strangers triggers oxytocin release and subsequent generosity. Ann N Y Acad Sci 182–9Google Scholar
  4. Barraza JA, McCullough ME, Ahmadi S, Zak PJ (2012) Oxytocin infusion increases charitable donations regardless of monetary resources. Horm Behav 60(2):148–151CrossRefGoogle Scholar
  5. Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E (2008) Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 58(4):639–650PubMedCrossRefGoogle Scholar
  6. Benelli A, Bertolini A, Poggioli R, Menozzi B, Basaglia R, Arletti R (1995) Polymodal dose–response curve for oxytocin in the social recognition test. Neuropeptides 28(4):251–255PubMedCrossRefGoogle Scholar
  7. Bester-Meredith JK, Young LJ, Marler CA (1999) Species differences in paternal behavior and aggression in Peromyscus and their associations with vasopressin immunoreactivity and receptors. Horm Behav 36(1):25–38PubMedCrossRefGoogle Scholar
  8. Bielsky IF, Young LJ (2004) Oxytocin, vasopressin, and social recognition in mammals. Peptides 25(9):1565–1574PubMedCrossRefGoogle Scholar
  9. Blanchard RJ, Griebel G, Farrokhi C, Markham C and Blanchard MY (2004) AVP V1b selective antagonist SSR149415 blocks aggressive behaviors in hamsters. . Pharmacology, Biochemistry and BehaviorGoogle Scholar
  10. Blume A, Bosch OJ, Miklos S, Torner L, Wales L, Waldherr M, Neumann ID (2008) Oxytocin reduces anxiety via ERK1/2 activation: local effect within the rat hypothalamic paraventricular nucleus. Eur J Neurosci 27(8):1947–1956PubMedCrossRefGoogle Scholar
  11. Bosch OJ (2011) Maternal nurturing is dependent on her innate anxiety: the behavioral roles of brain oxytocin and vasopressin. Horm Behav 59(2):202–212PubMedCrossRefGoogle Scholar
  12. Bosch OJ, Neumann ID (2012) Both oxytocin and vasopressin are mediators of maternal care and aggression in rodents: from central release to sites of action. Horm Behav 61(3):293–303PubMedCrossRefGoogle Scholar
  13. Bosch OJ, Kromer SA, Brunton PJ, Neumann ID (2004) 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 124(2):439–448PubMedCrossRefGoogle Scholar
  14. Bosch OJ, Meddle SL, Beiderbeck DI, Douglas AJ, Neumann ID (2005) Brain oxytocin correlates with maternal aggression: link to anxiety. J Neurosci 25(29):6807–6815PubMedCrossRefGoogle Scholar
  15. Bosch OJ, Pfortsch J, Beiderbeck DI, Landgraf R, Neumann ID (2010) Maternal behaviour is associated with vasopressin release in the medial preoptic area and bed nucleus of the stria terminalis in the rat. J Neuroendocrinol 22(5):420–429PubMedCrossRefGoogle Scholar
  16. Campbell A (2008) Attachment, aggression and affiliation: the role of oxytocin in female social behavior. Biol Psychol 77(1):1–10PubMedCrossRefGoogle Scholar
  17. Chini B, Manning M, Guillon G (2008) Affinity and efficacy of selective agonists and antagonists for vasopressin and oxytocin receptors: an “easy guide” to receptor pharmacology. Prog Brain Res 170:513–517PubMedCrossRefGoogle Scholar
  18. Cho MM, DeVries AC, Williams JR, Carter CS (1999) The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). Behav Neurosci 113(5):1071–1079PubMedCrossRefGoogle Scholar
  19. Choleris E, Clipperton-Allen AE, Phan A, Kavaliers M (2009) Neuroendocrinology of social information processing in rats and mice. Front Neuroendocrinol 30(4):442–459PubMedCrossRefGoogle Scholar
  20. Churchland PS, Winkielman P (2012) Modulating social behavior with oxytocin: how does it work? What does it mean? Hormones and Behavior(0)Google Scholar
  21. Coccaro EF, Kavoussi RJ, Hauger RL, Cooper TB, Ferris CF (1998) Cerebrospinal fluid vasopressin levels: correlates with aggression and serotonin function in personality-disordered subjects. Arch Gen Psychiatry 55(8):708–714PubMedCrossRefGoogle Scholar
  22. Compaan JC, Buijs RM, Pool CW, De Ruiter AJH, Koolhaas JM (1993) Differential lateral septal vasopressin innervation in aggressive and nonaggressive male mice. Brain Res Bull 30(1–2):1–6PubMedCrossRefGoogle Scholar
  23. Consiglio AR, Borsoi A, Pereira GAM, Lucion AB (2005) Effects of oxytocin microinjected into the central amygdaloid nucleus and bed nucleus of stria terminalis on maternal aggressive behavior in rats. Physiol Behav 85(3):354–362PubMedCrossRefGoogle Scholar
  24. Crawley JN, Chen T, Puri A, Washburn R, Sullivan TL, Hill JM, Young NB, Nadler JJ, Moy SS, Young LJ, Caldwell HK, Young WS (2007) Social approach behaviors in oxytocin knockout mice: comparison of two independent lines tested in different laboratory environments. Neuropeptides 41(3):145–163PubMedCrossRefGoogle Scholar
  25. de Boer SF, van der Vegt BJ, Koolhaas JM (2003) Individual variation in aggression of feral rodent strains: a standard for the genetics of aggression and violence? Behav Genet 33(5):485–501PubMedCrossRefGoogle Scholar
  26. de Boer SF, Caramaschi D, Natarajan D, Koolhaas JM (2009) The vicious cycle towards violence: focus on the negative feedback mechanisms of brain serotonin neurotransmission. Front Behav Neurosci 3(52):20Google Scholar
  27. De Dreu CKW (2011) Oxytocin modulates the link between adult attachment and cooperation through reduced betrayal aversion. Psychoneuroendocrinology(0)Google Scholar
  28. De Dreu CKW (2012) Oxytocin modulates cooperation within and competition between groups: an integrative review and research agenda. Horm Behav 61(3):419–428PubMedCrossRefGoogle Scholar
  29. De Dreu CKW, Greer LL, Van Kleef GA, Shalvi S, Handgraaf MJJ (2011) Oxytocin promotes human ethnocentrism. Proc Natl Acad Sci 108(4):1262–1266PubMedCrossRefGoogle Scholar
  30. De Vries AC, Young WS, Nelson RJ (1997) Reduced aggressive behaviour in mice with targeted disruption of the oxytocin gene. J Neuroendocrinol 9(5):363–368Google Scholar
  31. Devarajan K, Rusak B (2004) Oxytocin levels in the plasma and cerebrospinal fluid of male rats: effects of circadian phase, light and stress. Neurosci Lett 367(2):144–147PubMedCrossRefGoogle Scholar
  32. Devarajan K, Marchant EG, Rusak B (2005) Circadian and light regulation of oxytocin and parvalbumin protein levels in the ciliated ependymal layer of the third ventricle in the C57 mouse. Neuroscience 134(2):539–547PubMedCrossRefGoogle Scholar
  33. Dhakar MB, Rich ME, Reno EL, Lee H-J, Caldwell HK (2012) Heightened aggressive behavior in mice with lifelong versus postweaning knockout of the oxytocin receptor. Horm Behav 62(1):86–92PubMedCrossRefGoogle Scholar
  34. Di Simplicio M, Massey-Chase R, Cowen P, Harmer C (2009) Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers. J Psychopharmacol 23(3):241–248PubMedCrossRefGoogle Scholar
  35. Ditzen B, Schaer M, Gabriel B, Bodenmann G, Ehlert U, Heinrichs M (2009) Intranasal oxytocin increases positive communication and reduces cortisol levels during couple conflict. Biol Psychiatry 65(9):728–731PubMedCrossRefGoogle Scholar
  36. Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC (2007) Oxytocin improves “mind-reading” in humans. Biol Psychiatry 61(6):731–733PubMedCrossRefGoogle Scholar
  37. Donaldson ZR, Young LJ (2008) Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322(5903):900–904PubMedCrossRefGoogle Scholar
  38. Drago F, Pedersen CA, Caldwell JD, Prange AJ Jr (1986) Oxytocin potently enhances novelty-induced grooming behavior in the rat. Brain Res 368(2):287–295PubMedCrossRefGoogle Scholar
  39. Ebner K, Bosch OJ, Kromer SA, Singewald N, Neumann ID (2005) Release of oxytocin in the rat central amygdala modulates stress-coping behavior and the release of excitatory amino acids. Neuropsychopharmacology 30(2):223–230PubMedCrossRefGoogle Scholar
  40. Everts HGJ, De Ruiter AJH, Koolhaas JM (1997) Differential lateral septal vasopressin in wild-type rats: correlation with aggression. Horm Behav 31(2):136–144PubMedCrossRefGoogle Scholar
  41. Feldman R (2012) Oxytocin and social affiliation in humans. Horm Behav 61(3):380–391PubMedCrossRefGoogle Scholar
  42. Ferguson JN, Aldag JM, Insel TR, Young LJ (2001) Oxytocin in the medial amygdala is essential for social recognition in the mouse. J Neurosci 21(20):8278–8285PubMedGoogle Scholar
  43. Ferris CF, Potegal M (1988) Vasopressin receptor blockade in the anterior hypothalamus suppresses aggression in hamsters. Physiol Behav 44(2):235–239PubMedCrossRefGoogle Scholar
  44. Ferris CF, Foote KB, Meltser HM, Plenby MG, Smith KL, Insel TR (1992) Oxytocin in the amygdala facilitates maternal aggression. Ann N Y Acad Sci 652(1):456–457PubMedCrossRefGoogle Scholar
  45. Fetissov SO, Hallman J, Nilsson I, Lefvert A-K, Oreland L, Hokfelt T (2006) Aggressive behavior linked to corticotropin-reactive autoantibodies. Biol Psychiatry 60(8):799–802PubMedCrossRefGoogle Scholar
  46. Gil M, Bhatt R, Picotte KB, Hull EM (2011) Oxytocin in the medial preoptic area facilitates male sexual behavior in the rat. Horm Behav 59(4):435–443PubMedCrossRefGoogle Scholar
  47. Gordon I, Zagoory-Sharon O, Leckman JF, Feldman R (2010) Oxytocin and the development of parenting in humans. Biol Psychiatry 68(4):377–382PubMedCrossRefGoogle Scholar
  48. Gregory S, Connelly J, Towers A, Johnson J, Biscocho D, Markunas C, Lintas C, Abramson R, Wright H, Ellis P, Langford C, Worley G, Delong GR, Murphy S, Cuccaro M, Persico A, Pericak-Vance M (2009) Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med 7(1):62PubMedCrossRefGoogle Scholar
  49. Guastella AJ, Mitchell PB, Dadds MR (2008) Oxytocin increases gaze to the eye region of human faces. Biol Psychiatry 63(1):3–5PubMedCrossRefGoogle Scholar
  50. Gurrieri F, Neri G (2009) Defective oxytocin function: a clue to understanding the cause of autism? BMC Med 7(1):63PubMedCrossRefGoogle Scholar
  51. Gutzler SJ, Karom M, Erwin WD, Albers HE (2010) Arginine-vasopressin and the regulation of aggression in female Syrian hamsters (Mesocricetus auratus). Eur J Neurosci 31(9):1655–1663PubMedGoogle Scholar
  52. Harmon AC, Huhman KL, Moore TO, Albers HE (2002) Oxytocin inhibits aggression in female Syrian hamsters. J Neuroendocrinol 14(12):963–969PubMedCrossRefGoogle Scholar
  53. Higashida H, Yokoyama S, Kikuchi M, Munesue T (2012) CD38 and its role in oxytocin secretion and social behavior. Horm Behav 61(3):351–358PubMedCrossRefGoogle Scholar
  54. Hurlemann R, Patin A, Onur OA, Cohen MX, Baumgartner T, Metzler S, Dziobek I, Gallinat J, Wagner M, Maier W, Kendrick KM (2010) Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans. J Neurosci 30(14):4999–5007PubMedCrossRefGoogle Scholar
  55. Jacob S, Brune CW, Carter CS, Leventhal BL, Lord C, Cook EH Jr (2007) Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett 417(1):6–9PubMedCrossRefGoogle Scholar
  56. Jokinen J, Chatzittofis A, Hellstrom C, Nordstrom P, Uvnas-Moberg K, Asberg M (2012) Low CSF oxytocin reflects high intent in suicide attempters. Psychoneuroendocrinology 37(4):482–490PubMedCrossRefGoogle Scholar
  57. Jones PM, Robinson IC (1982) Differential clearance of neurophysin and neurohypophysial peptides from the cerebrospinal fluid in conscious guinea pigs. Neuroendocrinology 34(4):297–302PubMedCrossRefGoogle Scholar
  58. Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 25(49):11489–11493PubMedCrossRefGoogle Scholar
  59. Knobloch HS, Charlet A, Hoffmann LC, Eliava M, Khrulev S, Cetin AH, Osten P, Schwarz MK, Seeburg PH, Stoop R, Grinevich V (2012) Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron 73(3):553–566PubMedCrossRefGoogle Scholar
  60. Koolhaas JM, Schuurman T, Wiepkema PR (1980) The organization of intraspecific agonistic behaviour in the rat. Prog Neurobiol 15(3):247–268PubMedCrossRefGoogle Scholar
  61. Koolhaas JM, de Boer SF, Coppens CM, Buwalda B (2010) Neuroendocrinology of coping styles: towards understanding the biology of individual variation. Front Neuroendocrinol 31(3):307–321PubMedCrossRefGoogle Scholar
  62. Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435(7042):673–676PubMedCrossRefGoogle Scholar
  63. Krueger F, Parasuraman R, Iyengar V, Thornburg M, Weel J, Lin M, Clarke E, McCabe K, Lipsky R (2012) Oxytocin receptor genetic variation promotes human trust behavior. Frontiers in Human Neuroscience 6Google Scholar
  64. Lee PR, Brady DL, Shapiro RA, Dorsa DM, Koenig JI (2005) Social interaction deficits caused by chronic phencyclidine administration are reversed by oxytocin. Neuropsychopharmacology 30(10):1883–1894PubMedCrossRefGoogle Scholar
  65. Lee H-J, Caldwell HK, Macbeth AH, Tolu SG, Young WS (2008) A conditional knockout mouse line of the oxytocin receptor. Endocrinology 149(7):3256–3263PubMedCrossRefGoogle Scholar
  66. Lee HJ, Macbeth AH, Pagani JH, Young WS 3rd (2009a) Oxytocin: the great facilitator of life. Prog Neurobiol 88(2):127–151PubMedGoogle Scholar
  67. Lee R, Ferris C, Van de Kar LD, Coccaro EF (2009b) Cerebrospinal fluid oxytocin, life history of aggression, and personality disorder. Psychoneuroendocrinology 34(10):1567–1573PubMedCrossRefGoogle Scholar
  68. Lerer E, Levi S, Salomon S, Darvasi A, Yirmiya N, Ebstein RP (2008) Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition. Mol Psychiatry 13(10):980–988PubMedCrossRefGoogle Scholar
  69. Linfoot I, Gray M, Bingham B, Williamson M, Pinel JP, Viau V (2009) Naturally occurring variations in defensive burying behavior are associated with differences in vasopressin, oxytocin, and androgen receptors in the male rat. Prog Neuropsychopharmacol Biol Psychiatry 33(7):1129–1140PubMedCrossRefGoogle Scholar
  70. Liu Y, Wang ZX (2003) Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles. Neuroscience 121(3):537–544PubMedCrossRefGoogle Scholar
  71. Luiten PG, Koolhaas JM, de Boer S, Koopmans SJ (1985) The cortico-medial amygdala in the central nervous system organization of agonistic behavior. Brain Res 332(2):283–297PubMedCrossRefGoogle Scholar
  72. MacDonald K, MacDonald TM (2010) The peptide that binds: a systematic review of oxytocin and its prosocial effects in humans. Harv Rev Psychiatry 18(1):1–21PubMedCrossRefGoogle Scholar
  73. Malik AI, Zai CC, Abu Z, Nowrouzi B, Beitchman JH (2012) The role of oxytocin and oxytocin receptor gene variants in childhood-onset aggression. Genes Brain Behav 11(5):545–551PubMedCrossRefGoogle Scholar
  74. Manning M, Sawyer WH (1989) Discovery, development, and some uses of vasopressin and oxytocin antagonists. J Lab Clin Med 114(6):617–632PubMedGoogle Scholar
  75. Manning M, Misicka A, Olma A, Bankowski K, Stoev S, Chini B, Durroux T, Mouillac B, Corbani M, Guillon G (2012) Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics. J Neuroendocrinol 24(4):609–628PubMedCrossRefGoogle Scholar
  76. Mens WB, Witter A, van Wimersma Greidanus TB (1983) Penetration of neurohypophyseal hormones from plasma into cerebrospinal fluid (CSF): half-times of disappearance of these neuropeptides from CSF. Brain Res 262(1):143–149PubMedCrossRefGoogle Scholar
  77. Naber F, van Ijzendoorn MH, Deschamps P, van Engeland H, Bakermans-Kranenburg MJ (2010) Intranasal oxytocin increases fathers’ observed responsiveness during play with their children: a double-blind within-subject experiment. Psychoneuroendocrinology 35(10):1583–1586PubMedCrossRefGoogle Scholar
  78. Neumann ID (2008) Brain oxytocin: a key regulator of emotional and social behaviours in both females and males. J Neuroendocrinol 20(6):858–865PubMedCrossRefGoogle Scholar
  79. Neumann ID, Kromer SA, Toschi N, Ebner K (2000) Brain oxytocin inhibits the (re)activity of the hypothalamo-pituitary-adrenal axis in male rats: involvement of hypothalamic and limbic brain regions. Regul Pept 96(1–2):31–38PubMedCrossRefGoogle Scholar
  80. Olivier B, Mos J, van Oorschot R, Hen R (1995) Serotonin receptors and animal models of aggressive behavior. Pharmacopsychiatry 28(S 2):80–90PubMedCrossRefGoogle Scholar
  81. Onaka T, Ikeda K, Yamashita T, Honda K (2003) Facilitative role of endogenous oxytocin in noradrenaline release in the rat supraoptic nucleus. Eur J Neurosci 18(11):3018–3026PubMedCrossRefGoogle Scholar
  82. Pobbe RLH, Pearson BL, Defensor EB, Bolivar VJ, Young Iii WS, Lee H-J, Blanchard DC, Blanchard RJ (2012) Oxytocin receptor knockout mice display deficits in the expression of autism-related behaviors. Horm Behav 61(3):436–444PubMedCrossRefGoogle Scholar
  83. Popik P, van Ree JM (1991) Oxytocin but not vasopressin facilities social recognition following injection into the medial preoptic area of the rat brain. Eur Neuropsychopharmacol 1(4):555–560PubMedCrossRefGoogle Scholar
  84. Popik P, Vetulani J (1991) Opposite action of oxytocin and its peptide antagonists on social memory in rats. Neuropeptides 18(1):23–27PubMedCrossRefGoogle Scholar
  85. Popik P, Vetulani J, van Ree JM (1992) Low doses of oxytocin facilitate social recognition in rats. Psychopharmacology 106(1):71–74PubMedCrossRefGoogle Scholar
  86. Ragnauth AK, Devidze N, Moy V, Finley K, Goodwillie A, Kow LM, Muglia LJ, Pfaff DW (2005) Female oxytocin gene-knockout mice, in a semi-natural environment, display exaggerated aggressive behavior. Genes Brain Behav 4(4):229–239PubMedCrossRefGoogle Scholar
  87. Riem MME, Bakermans-Kranenburg MJ, Pieper S, Tops M, Boksem MAS, Vermeiren RRJM, van Ijzendoorn MH, Rombouts SARB (2011) Oxytocin modulates amygdala, insula, and inferior frontal gyrus responses to infant crying: a randomized controlled trial. Biol Psychiatry 70(3):291–297PubMedCrossRefGoogle Scholar
  88. Rimmele U, Hediger K, Heinrichs M, Klaver P (2009) Oxytocin makes a face in memory familiar. J Neurosci 29(1):38–42PubMedCrossRefGoogle Scholar
  89. Robinson IC, Jones PM (1982) Oxytocin and neurophysin in plasma and CSF during suckling in the guinea-pig. Neuroendocrinology 34(1):59–63PubMedCrossRefGoogle Scholar
  90. Ross HE, Young LJ (2009) Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Front Neuroendocrinol 30(4):534–547PubMedCrossRefGoogle Scholar
  91. Sala M, Braida D, Lentini D, Busnelli M, Bulgheroni E, Capurro V, Finardi A, Donzelli A, Pattini L, Rubino T, Parolaro D, Nishimori K, Parenti M, Chini B (2011) Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: a neurobehavioral model of autism. Biol Psychiatry 69(9):875–882PubMedCrossRefGoogle Scholar
  92. Sala M, Braida D, Donzelli A, Martucci R, Busnelli M, Bulgheroni E, Rubino T, Parolaro D, Nishimori K, Chini B (2012) Mice heterozygous for the oxytocin receptor gene (Oxtr(+/−)) show impaired social behaviour but not increased aggression or cognitive inflexibility: evidence of a selective haploinsufficiency gene effect. J Neuroendocrinol 25(2):107–118CrossRefGoogle Scholar
  93. Silakov VL, Nikitin VS, Moiseeva LA, Losev SS, Perepelkin PD (1992) The comparative action of relanium and oxytocin on higher nervous activity in lower monkeys. Zh Vyssh Nerv Deiat Im I P Pavlova 42(4):734–742PubMedGoogle Scholar
  94. Snowdon CT, Pieper BA, Boe CY, Cronin KA, Kurian AV, Ziegler TE (2010) Variation in oxytocin is related to variation in affiliative behavior in monogamous, pairbonded tamarins. Horm Behav 58(4):614–618PubMedCrossRefGoogle Scholar
  95. Strathearn L (2011) Maternal neglect: oxytocin, dopamine and the neurobiology of attachment. J Neuroendocrinol 23(11):1054–1065PubMedCrossRefGoogle Scholar
  96. Striepens N, Kendrick KM, Maier W, Hurlemann R (2011) Prosocial effects of oxytocin and clinical evidence for its therapeutic potential. Front Neuroendocrinol 32(4):426–450PubMedCrossRefGoogle Scholar
  97. Takayanagi Y, Yoshida M, Bielsky IF, Ross HE, Kawamata M, Onaka T, Yanagisawa T, Kimura T, Matzuk MM, Young LJ, Nishimori K (2005) Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proc Natl Acad Sci U S A 102(44):16096–16101PubMedCrossRefGoogle Scholar
  98. Theodoridou A, Rowe AC, Penton-Voak IS, Rogers PJ (2009) Oxytocin and social perception: oxytocin increases perceived facial trustworthiness and attractiveness. Horm Behav 56(1):128–132PubMedCrossRefGoogle Scholar
  99. Tobin VA, Hashimoto H, Wacker DW, Takayanagi Y, Langnaese K, Caquineau C, Noack J, Landgraf R, Onaka T, Leng G, Meddle SL, Engelmann M, Ludwig M (2010) An intrinsic vasopressin system in the olfactory bulb is involved in social recognition. Nature 464(7287):413–417PubMedCrossRefGoogle Scholar
  100. Van Den Berg CL, Van Ree JM, Spruijt BM (1999) Sequential analysis of juvenile isolation-induced decreased social behavior in the adult rat. Physiology Behav 67(4):483–488CrossRefGoogle Scholar
  101. Veening JG, Coolen LM, de Jong TR, Joosten HW, de Boer SF, Koolhaas JM, Olivier B (2005) Do similar neural systems subserve aggressive and sexual behaviour in male rats? Insights from c-Fos and pharmacological studies. Eur J Pharmacol 526(1–3):226–239PubMedCrossRefGoogle Scholar
  102. Veening JG, de Jong T, Barendregt HP (2010) Oxytocin-messages via the cerebrospinal fluid: behavioral effects; a review. Physiol Behav 101(2):193–210PubMedCrossRefGoogle Scholar
  103. Wermter A-K, Kamp-Becker I, Hesse P, Schulte-Körne G, Strauch K, Remschmidt H (2010) 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 Neuropsychiatric Genetics 153B(2):629–639Google Scholar
  104. Williams JR, Insel TR, Harbaugh CR, Carter CS (1994a) Oxytocin administered centrally facilitates formation of a partner preference in female prairie voles (Microtus ochrogaster). J Neuroendocrinol 6(3):247–250PubMedCrossRefGoogle Scholar
  105. Williams PD, Anderson PS, Ball RG, Bock MG, Carroll L, Chiu S-HL, Clineschmidt BV, Culberson JC, Erb JM (1994b) 1-(((7,7-Dimethyl-2(S)-(2(S)-amino-4-(methylsulfonyl)butyramido)bicyclo[2.2.1]heptan-1(S)-yl)methyl)sulfonyl)-4-(2-methylphenyl)piperazine (L-368,899): an orally bioavailable, non-peptide oxytocin antagonist with potential utility for managing preterm labor. J Med Chem 37(5):565–571PubMedCrossRefGoogle Scholar
  106. Winslow J, Insel T (1991) Social status in pairs of male squirrel monkeys determines the behavioral response to central oxytocin administration. J Neurosci 11(7):2032–2038PubMedGoogle Scholar
  107. Winslow JT, Hastings N, Carter CS, Harbaugh CR, Insel TR (1993a) A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 365(6446):545–548PubMedCrossRefGoogle Scholar
  108. Winslow JT, Shapiro L, Carter CS, Insel TR (1993b) Oxytocin and complex social behavior: species comparisons. Psychopharmacol Bull 29(3):409–414PubMedGoogle Scholar
  109. Winslow JT, Hearn EF, Ferguson J, Young LJ, Matzuk MM, Insel TR (2000) Infant vocalization, adult aggression, and fear behavior of an oxytocin null mutant mouse. Horm Behav 37(2):145–155PubMedCrossRefGoogle Scholar
  110. Witt DM, Sue Carter C, Walton DM (1990) Central and peripheral effects of oxytocin administration in prairie voles (Microtus ochrogaster). Pharmacol Biochem Behav 37(1):63–69PubMedCrossRefGoogle Scholar
  111. Witt DM, Winslow JT, Insel TR (1992) Enhanced social interactions in rats following chronic, centrally infused oxytocin. Pharmacol Biochem Behav 43(3):855–861PubMedCrossRefGoogle Scholar
  112. Wu S, Jia M, Ruan Y, Liu J, Guo Y, Shuang M, Gong X, Zhang Y, Yang X, Zhang D (2005) Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol Psychiatry 58(1):74–77PubMedCrossRefGoogle Scholar
  113. Wu N, Li Z, Su Y (2012) The association between oxytocin receptor gene polymorphism (OXTR) and trait empathy. J Affect Disord 138(3):468–472PubMedCrossRefGoogle Scholar
  114. Yu H, Yue P, Sun P, Zhao X (2010) Self-grooming induced by sexual chemical signals in male root voles (Microtus oeconomus Pallas). Behav Process 83(3):292–298CrossRefGoogle Scholar
  115. Zak PJ, Stanton AA, Ahmadi S (2007) Oxytocin increases generosity in humans. PLoS One 2(11):e1128PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Federica Calcagnoli
    • 1
    • 3
  • Sietse F. de Boer
    • 1
  • Monika Althaus
    • 2
  • Johan A. den Boer
    • 3
  • Jaap M. Koolhaas
    • 1
  1. 1.Department of Behavioral PhysiologyUniversity of GroningenGroningenThe Netherlands
  2. 2.Child and Adolescent PsychiatryUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
  3. 3.Department of PsychiatryUniversity Medical Center GroningenGroningenThe Netherlands

Personalised recommendations