Skip to main content

Advertisement

SpringerLink
Log in

Antiaggressive activity of central oxytocin in male rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

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.

Objective

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.

Methods

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.

Results

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • 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):9–20

    Article  PubMed  CAS  Google Scholar 

  • 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):178–184

    Article  PubMed  CAS  Google Scholar 

  • Barraza JA, Zak PJ (2009) Empathy toward strangers triggers oxytocin release and subsequent generosity. Ann N Y Acad Sci 182–9

  • Barraza JA, McCullough ME, Ahmadi S, Zak PJ (2012) Oxytocin infusion increases charitable donations regardless of monetary resources. Horm Behav 60(2):148–151

    Article  CAS  Google Scholar 

  • 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):639–650

    Article  PubMed  CAS  Google Scholar 

  • 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):251–255

    Article  PubMed  CAS  Google Scholar 

  • 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):25–38

    Article  PubMed  CAS  Google Scholar 

  • Bielsky IF, Young LJ (2004) Oxytocin, vasopressin, and social recognition in mammals. Peptides 25(9):1565–1574

    Article  PubMed  CAS  Google Scholar 

  • 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 Behavior

  • 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):1947–1956

    Article  PubMed  Google Scholar 

  • Bosch OJ (2011) Maternal nurturing is dependent on her innate anxiety: the behavioral roles of brain oxytocin and vasopressin. Horm Behav 59(2):202–212

    Article  PubMed  CAS  Google Scholar 

  • 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):293–303

    Article  PubMed  CAS  Google Scholar 

  • 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):439–448

    Article  PubMed  CAS  Google Scholar 

  • Bosch OJ, Meddle SL, Beiderbeck DI, Douglas AJ, Neumann ID (2005) Brain oxytocin correlates with maternal aggression: link to anxiety. J Neurosci 25(29):6807–6815

    Article  PubMed  CAS  Google Scholar 

  • 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):420–429

    Article  PubMed  CAS  Google Scholar 

  • Campbell A (2008) Attachment, aggression and affiliation: the role of oxytocin in female social behavior. Biol Psychol 77(1):1–10

    Article  PubMed  Google Scholar 

  • 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 170:513–517

    Article  PubMed  CAS  Google Scholar 

  • 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):1071–1079

    Article  PubMed  CAS  Google Scholar 

  • Choleris E, Clipperton-Allen AE, Phan A, Kavaliers M (2009) Neuroendocrinology of social information processing in rats and mice. Front Neuroendocrinol 30(4):442–459

    Article  PubMed  CAS  Google Scholar 

  • Churchland PS, Winkielman P (2012) Modulating social behavior with oxytocin: how does it work? What does it mean? Hormones and Behavior(0)

  • 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):708–714

    Article  PubMed  CAS  Google Scholar 

  • 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):1–6

    Article  PubMed  CAS  Google Scholar 

  • 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):354–362

    Article  PubMed  CAS  Google Scholar 

  • 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):145–163

    Article  PubMed  CAS  Google Scholar 

  • 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):485–501

    Article  PubMed  Google Scholar 

  • 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):20

    Google Scholar 

  • De Dreu CKW (2011) Oxytocin modulates the link between adult attachment and cooperation through reduced betrayal aversion. Psychoneuroendocrinology(0)

  • De Dreu CKW (2012) Oxytocin modulates cooperation within and competition between groups: an integrative review and research agenda. Horm Behav 61(3):419–428

    Article  PubMed  CAS  Google Scholar 

  • De Dreu CKW, Greer LL, Van Kleef GA, Shalvi S, Handgraaf MJJ (2011) Oxytocin promotes human ethnocentrism. Proc Natl Acad Sci 108(4):1262–1266

    Article  PubMed  Google Scholar 

  • De Vries AC, Young WS, Nelson RJ (1997) Reduced aggressive behaviour in mice with targeted disruption of the oxytocin gene. J Neuroendocrinol 9(5):363–368

    Google Scholar 

  • 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):144–147

    Article  PubMed  CAS  Google Scholar 

  • 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):539–547

    Article  PubMed  CAS  Google Scholar 

  • 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):86–92

    Article  PubMed  CAS  Google Scholar 

  • 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):241–248

    Article  PubMed  Google Scholar 

  • 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):728–731

    Article  PubMed  CAS  Google Scholar 

  • Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC (2007) Oxytocin improves “mind-reading” in humans. Biol Psychiatry 61(6):731–733

    Article  PubMed  CAS  Google Scholar 

  • Donaldson ZR, Young LJ (2008) Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322(5903):900–904

    Article  PubMed  CAS  Google Scholar 

  • Drago F, Pedersen CA, Caldwell JD, Prange AJ Jr (1986) Oxytocin potently enhances novelty-induced grooming behavior in the rat. Brain Res 368(2):287–295

    Article  PubMed  CAS  Google Scholar 

  • 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):223–230

    Article  PubMed  CAS  Google Scholar 

  • Everts HGJ, De Ruiter AJH, Koolhaas JM (1997) Differential lateral septal vasopressin in wild-type rats: correlation with aggression. Horm Behav 31(2):136–144

    Article  PubMed  CAS  Google Scholar 

  • Feldman R (2012) Oxytocin and social affiliation in humans. Horm Behav 61(3):380–391

    Article  PubMed  CAS  Google Scholar 

  • 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):8278–8285

    PubMed  CAS  Google Scholar 

  • Ferris CF, Potegal M (1988) Vasopressin receptor blockade in the anterior hypothalamus suppresses aggression in hamsters. Physiol Behav 44(2):235–239

    Article  PubMed  CAS  Google Scholar 

  • 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):456–457

    Article  PubMed  CAS  Google Scholar 

  • 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):799–802

    Article  PubMed  CAS  Google Scholar 

  • 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):435–443

    Article  PubMed  CAS  Google Scholar 

  • Gordon I, Zagoory-Sharon O, Leckman JF, Feldman R (2010) Oxytocin and the development of parenting in humans. Biol Psychiatry 68(4):377–382

    Article  PubMed  CAS  Google Scholar 

  • 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):62

    Article  PubMed  CAS  Google Scholar 

  • Guastella AJ, Mitchell PB, Dadds MR (2008) Oxytocin increases gaze to the eye region of human faces. Biol Psychiatry 63(1):3–5

    Article  PubMed  CAS  Google Scholar 

  • Gurrieri F, Neri G (2009) Defective oxytocin function: a clue to understanding the cause of autism? BMC Med 7(1):63

    Article  PubMed  CAS  Google Scholar 

  • 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):1655–1663

    PubMed  Google Scholar 

  • Harmon AC, Huhman KL, Moore TO, Albers HE (2002) Oxytocin inhibits aggression in female Syrian hamsters. J Neuroendocrinol 14(12):963–969

    Article  PubMed  CAS  Google Scholar 

  • Higashida H, Yokoyama S, Kikuchi M, Munesue T (2012) CD38 and its role in oxytocin secretion and social behavior. Horm Behav 61(3):351–358

    Article  PubMed  CAS  Google Scholar 

  • 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):4999–5007

    Article  PubMed  CAS  Google Scholar 

  • 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):6–9

    Article  PubMed  CAS  Google Scholar 

  • 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):482–490

    Article  PubMed  CAS  Google Scholar 

  • Jones PM, Robinson IC (1982) Differential clearance of neurophysin and neurohypophysial peptides from the cerebrospinal fluid in conscious guinea pigs. Neuroendocrinology 34(4):297–302

    Article  PubMed  CAS  Google Scholar 

  • 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):11489–11493

    Article  PubMed  CAS  Google Scholar 

  • 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):553–566

    Article  PubMed  CAS  Google Scholar 

  • Koolhaas JM, Schuurman T, Wiepkema PR (1980) The organization of intraspecific agonistic behaviour in the rat. Prog Neurobiol 15(3):247–268

    Article  PubMed  CAS  Google Scholar 

  • 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):307–321

    Article  PubMed  CAS  Google Scholar 

  • Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435(7042):673–676

    Article  PubMed  CAS  Google Scholar 

  • 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 6

  • 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):1883–1894

    Article  PubMed  CAS  Google Scholar 

  • Lee H-J, Caldwell HK, Macbeth AH, Tolu SG, Young WS (2008) A conditional knockout mouse line of the oxytocin receptor. Endocrinology 149(7):3256–3263

    Article  PubMed  CAS  Google Scholar 

  • Lee HJ, Macbeth AH, Pagani JH, Young WS 3rd (2009a) Oxytocin: the great facilitator of life. Prog Neurobiol 88(2):127–151

    PubMed  CAS  Google Scholar 

  • Lee R, Ferris C, Van de Kar LD, Coccaro EF (2009b) Cerebrospinal fluid oxytocin, life history of aggression, and personality disorder. Psychoneuroendocrinology 34(10):1567–1573

    Article  PubMed  CAS  Google Scholar 

  • 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):980–988

    Article  PubMed  CAS  Google Scholar 

  • 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):1129–1140

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Wang ZX (2003) Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles. Neuroscience 121(3):537–544

    Article  PubMed  CAS  Google Scholar 

  • 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):283–297

    Article  PubMed  CAS  Google Scholar 

  • 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):1–21

    Article  PubMed  Google Scholar 

  • 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):545–551

    Article  PubMed  CAS  Google Scholar 

  • Manning M, Sawyer WH (1989) Discovery, development, and some uses of vasopressin and oxytocin antagonists. J Lab Clin Med 114(6):617–632

    PubMed  CAS  Google Scholar 

  • 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):609–628

    Article  PubMed  CAS  Google Scholar 

  • 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):143–149

    Article  PubMed  CAS  Google Scholar 

  • 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):1583–1586

    Article  PubMed  CAS  Google Scholar 

  • Neumann ID (2008) Brain oxytocin: a key regulator of emotional and social behaviours in both females and males. J Neuroendocrinol 20(6):858–865

    Article  PubMed  CAS  Google Scholar 

  • 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):31–38

    Article  PubMed  CAS  Google Scholar 

  • Olivier B, Mos J, van Oorschot R, Hen R (1995) Serotonin receptors and animal models of aggressive behavior. Pharmacopsychiatry 28(S 2):80–90

    Article  PubMed  Google Scholar 

  • 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):3018–3026

    Article  PubMed  Google Scholar 

  • 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):436–444

    Article  PubMed  CAS  Google Scholar 

  • 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):555–560

    Article  PubMed  CAS  Google Scholar 

  • Popik P, Vetulani J (1991) Opposite action of oxytocin and its peptide antagonists on social memory in rats. Neuropeptides 18(1):23–27

    Article  PubMed  CAS  Google Scholar 

  • Popik P, Vetulani J, van Ree JM (1992) Low doses of oxytocin facilitate social recognition in rats. Psychopharmacology 106(1):71–74

    Article  PubMed  CAS  Google Scholar 

  • 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):229–239

    Article  PubMed  CAS  Google Scholar 

  • 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):291–297

    Article  PubMed  CAS  Google Scholar 

  • Rimmele U, Hediger K, Heinrichs M, Klaver P (2009) Oxytocin makes a face in memory familiar. J Neurosci 29(1):38–42

    Article  PubMed  CAS  Google Scholar 

  • Robinson IC, Jones PM (1982) Oxytocin and neurophysin in plasma and CSF during suckling in the guinea-pig. Neuroendocrinology 34(1):59–63

    Article  PubMed  CAS  Google Scholar 

  • Ross HE, Young LJ (2009) Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Front Neuroendocrinol 30(4):534–547

    Article  PubMed  CAS  Google Scholar 

  • 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):875–882

    Article  PubMed  CAS  Google Scholar 

  • 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):107–118

    Article  CAS  Google Scholar 

  • 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):734–742

    PubMed  CAS  Google Scholar 

  • 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):614–618

    Article  PubMed  CAS  Google Scholar 

  • Strathearn L (2011) Maternal neglect: oxytocin, dopamine and the neurobiology of attachment. J Neuroendocrinol 23(11):1054–1065

    Article  PubMed  CAS  Google Scholar 

  • Striepens N, Kendrick KM, Maier W, Hurlemann R (2011) Prosocial effects of oxytocin and clinical evidence for its therapeutic potential. Front Neuroendocrinol 32(4):426–450

    Article  PubMed  CAS  Google Scholar 

  • 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):16096–16101

    Article  PubMed  CAS  Google Scholar 

  • 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):128–132

    Article  PubMed  CAS  Google Scholar 

  • 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):413–417

    Article  PubMed  CAS  Google Scholar 

  • 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):483–488

    Article  Google Scholar 

  • 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):226–239

    Article  PubMed  CAS  Google Scholar 

  • Veening JG, de Jong T, Barendregt HP (2010) Oxytocin-messages via the cerebrospinal fluid: behavioral effects; a review. Physiol Behav 101(2):193–210

    Article  PubMed  CAS  Google Scholar 

  • 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):629–639

    CAS  Google Scholar 

  • 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):247–250

    Article  PubMed  CAS  Google Scholar 

  • 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):565–571

    Article  PubMed  CAS  Google Scholar 

  • 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):2032–2038

    PubMed  CAS  Google Scholar 

  • 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):545–548

    Article  PubMed  CAS  Google Scholar 

  • Winslow JT, Shapiro L, Carter CS, Insel TR (1993b) Oxytocin and complex social behavior: species comparisons. Psychopharmacol Bull 29(3):409–414

    PubMed  CAS  Google Scholar 

  • 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):145–155

    Article  PubMed  CAS  Google Scholar 

  • 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):63–69

    Article  PubMed  CAS  Google Scholar 

  • Witt DM, Winslow JT, Insel TR (1992) Enhanced social interactions in rats following chronic, centrally infused oxytocin. Pharmacol Biochem Behav 43(3):855–861

    Article  PubMed  CAS  Google Scholar 

  • 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):74–77

    Article  PubMed  CAS  Google Scholar 

  • Wu N, Li Z, Su Y (2012) The association between oxytocin receptor gene polymorphism (OXTR) and trait empathy. J Affect Disord 138(3):468–472

    Article  PubMed  CAS  Google Scholar 

  • 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):292–298

    Article  Google Scholar 

  • Zak PJ, Stanton AA, Ahmadi S (2007) Oxytocin increases generosity in humans. PLoS One 2(11):e1128

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

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

Author information

Authors and Affiliations

  1. Department of Behavioral Physiology, University of Groningen, P.O. Box 11103, 9700 CC, Groningen, The Netherlands

    Federica Calcagnoli, Sietse F. de Boer & Jaap M. Koolhaas

  2. Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    Monika Althaus

  3. Department of Psychiatry, University Medical Center Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands

    Federica Calcagnoli & Johan A. den Boer

Authors
  1. Federica Calcagnoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sietse F. de Boer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monika Althaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Johan A. den Boer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jaap M. Koolhaas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Federica Calcagnoli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Calcagnoli, F., de Boer, S.F., Althaus, M. et al. Antiaggressive activity of central oxytocin in male rats. Psychopharmacology 229, 639–651 (2013). https://doi.org/10.1007/s00213-013-3124-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-013-3124-7

Keywords

Search

Navigation