Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Research Article
  • Published:

Vasopressin V1b receptor knockout reduces aggressive behavior in male mice

Molecular Psychiatry volume 7, pages 975–984 (2002)Cite this article

Abstract

Increased aggression is commonly associated with many neurological and psychiatric disorders. Current treatments are largely empirical and are often accompanied by severe side effects, underscoring the need for a better understanding of the neural bases of aggression. Vasopressin, acting through its 1a receptor subtype, is known to affect aggressive behaviors. The vasopressin 1b receptor (V1bR) is also expressed in the brain, but has received much less attention due to a lack of specific drugs. Here we report that mice without the V1bR exhibit markedly reduced aggression and modestly impaired social recognition. By contrast, they perform normally in all the other behaviors that we have examined, such as sexual behavior, suggesting that reduced aggression and social memory are not simply the result of a global deficit in sensorimotor function or motivation. Fos-mapping within chemosensory responsive regions suggests that the behavioral deficits in V1bR knockout mice are not due to defects in detection and transmission of chemosensory signals to the brain. We suggest that V1bR antagonists could prove useful for treating aggressive behavior seen, for example, in dementias and traumatic brain injuries.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Saver JL, Salloway SP, Devinsky O, Bear DM . Neuropsychiatry of aggression. In: Fogel BS, Schiffer RB, Rao SM. (eds) Neuropsychiatry Williams & Wilkins: Baltimore 1996 523–548

    Google Scholar 

  2. Rosenblatt A, Leroi I . Neuropsychiatry of Huntington's disease and other basal ganglia disorders Psychosomatics 2000 41: 24–30

    Article  CAS  PubMed  Google Scholar 

  3. Yeager CA, Lewis DO . Mental illness, neuropsychologic deficits, child abuse, and violence Child Adolesc Psychiatr Clin N Am 2000 9: 793–813

    Article  CAS  PubMed  Google Scholar 

  4. Filley CM, Price BH, Nell V, Antoinette T, Morgan AS, Bresnahan JF et al. Toward an understanding of violence: neurobehavioral aspects of unwarranted physical aggression: Aspen Neurobehavioral Conference consensus statement Neuropsychiatry Neuropsychol Behav Neurol 2001 14: 1–14

    CAS  PubMed  Google Scholar 

  5. Tune LE . Risperidone for the treatment of behavioral and psychological symptoms of dementia J Clin Psychiatry 2001 62 Suppl 21: 29–32

    CAS  PubMed  Google Scholar 

  6. Goodson JL, Bass AH . Social behavior functions and related anatomical characteristics of vasotocin/vasopressin systems in vertebrates Brain Res Rev 2001 35: 246–265

    Article  CAS  PubMed  Google Scholar 

  7. Moore FL, Lowry CA, Rose JD . Steroid-neuropeptide interactions that control reproductive behaviors in an amphibian Psychoneuroendocrinology 1994 19: 581–592

    Article  CAS  PubMed  Google Scholar 

  8. Ferris CF, Delville Y . Vasopressin and serotonin interactions in the control of agonistic behavior Psychoneuroendocrinology 1994 19: 593–601

    Article  CAS  PubMed  Google Scholar 

  9. Semsar K, Kandel FL, Godwin J . Manipulations of the AVT system shift social status and related courtship and aggressive behavior in the bluehead wrasse Horm Behav 2001 40: 21–31

    Article  CAS  PubMed  Google Scholar 

  10. Koolhaas JM, Everts H, de Ruiter AJ, de Boer SF, Bohus B . Coping with stress in rats and mice: differential peptidergic modulation of the amygdala-lateral septum complex Prog Brain Res 1998 119: 437–448

    Article  CAS  PubMed  Google Scholar 

  11. 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

    Article  CAS  PubMed  Google Scholar 

  12. Coccaro EF, Kavoussi RJ, Hauger RL, Cooper TB, Ferris CF . Cerebrospinal fluid vasopressin levels: correlates with aggression and serotonin function in personality-disordered subjects Arch Gen Psychiatry 1998 55: 708–714

    Article  CAS  PubMed  Google Scholar 

  13. Popik PP, Vos PEP, Van Ree JMJ . Neurohypophyseal hormone receptors in the septum are implicated in social recognition in the rat Behav Pharmacol 1992 3: 351–358

    Article  CAS  PubMed  Google Scholar 

  14. Dluzen DE, Muraoka S, Engelmann M, Landgraf R . The effects of infusion of arginine vasopressin, oxytocin, or their antagonists into the olfactory bulb upon social recognition responses in male rats Peptides 1998 19: 999–1005

    Article  CAS  PubMed  Google Scholar 

  15. Engelmann M, Wotjak CT, Ebner K, Landgraf R . Behavioural impact of intraseptally released vasopressin and oxytocin in rats Exp Physiol 2000 85: 125S–130S

    Article  CAS  PubMed  Google Scholar 

  16. Dantzer R . Vasopressin, gonadal steroids and social recognition Prog Brain Res 1998 119: 409–414

    Article  CAS  PubMed  Google Scholar 

  17. Alescio-Lautier B, Rao H, Paban V, Devigne C, Soumireu-Mourat B . Inhibition of the vasopressin-enhancing effect on memory retrieval and relearning by a vasopressin V1 receptor antagonist in mice Eur J Pharmacol 1995 294: 763–770

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Everts HG, 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 15: 7–16

    Article  Google Scholar 

  20. Lolait SJ, O'Carroll AM, Mahan LC, Felder CC, Button D, Young WS III et al. Extrapituitary expression of the rat V1b vasopressin receptor gene Proc Natl Acad Sci 1995 92: 6783–6787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hernando F, Schoots O, Lolait SJ, Burbach JP . 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: 1659–1668

    Article  CAS  PubMed  Google Scholar 

  22. Tybulewicz VL, Crawford CE, Jackson PK, Bronson RT, Mulligan RC . Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene Cell 1991 65: 1153–1163

    Article  CAS  PubMed  Google Scholar 

  23. Crawley JN . What's Wrong With My Mouse: Behavioral Phenotyping of Transgenic and Knockout Mice Wiley-Liss: New York 2000

    Google Scholar 

  24. Nelson RJ, Chiavegatto S . Molecular basis of aggression Trends Neurosci 2001 24: 713–719

    Article  CAS  PubMed  Google Scholar 

  25. Ferris CF, Melloni RH Jr, Koppel G, Perry KW, Fuller RW, Delville Y . Vasopressin/serotonin interactions in the anterior hypothalamus control aggressive behavior in golden hamsters J Neurosci 1997 17: 4331–4340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ferris CF . Adolescent stress and neural plasticity in hamsters: a vasopressin-serotonin model of inappropriate aggressive behaviour Exp Physiol 2000 85: 85S–90S

    Article  CAS  PubMed  Google Scholar 

  27. Beeman EA . The effect of male hormone on aggressive behavior in mice Physiol Zool 1947 20: 373–405

    Article  CAS  PubMed  Google Scholar 

  28. Parmigiani S, Palanza P, Rogers J, Ferrari PF . Selection, evolution of behavior and animal models in behavioral neuroscience Neurosci Biobehav Rev 1999 23: 957–970

    Article  CAS  PubMed  Google Scholar 

  29. Delville Y, Mansour KM, Ferris CF . Serotonin blocks vasopressin-facilitated offensive aggression: interactions within the ventrolateral hypothalamus of golden hamsters Physiol Behav 1996 59: 813–816

    Article  CAS  PubMed  Google Scholar 

  30. Lister RG . The use of a plus-maze to measure anxiety in the mouse Psychopharmacology 1987 92: 180–185

    CAS  PubMed  Google Scholar 

  31. Holmes A . Targeted gene mutation approaches to the study of anxiety-like behavior in mice Neurosci Biobehav Rev 2001 25: 261–273

    Article  CAS  PubMed  Google Scholar 

  32. Saito M, Sugimoto T, Tahara A, Kawashima H . 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

    Article  CAS  PubMed  Google Scholar 

  33. Vaccari C, Lolait SJ, Ostrowski NL . Comparative distribution of vasopressin V1b and oxytocin receptor messenger ribonucleic acids in brain Endocrinology 1998 139: 5015–5033

    Article  CAS  PubMed  Google Scholar 

  34. Bronson FH . Rodent pheromones Biol Reprod 1971 4: 344–357

    CAS  PubMed  Google Scholar 

  35. Schultz EF, Tapp JT . Olfactory control of behavior in rodents Psychol Bull 1973 79: 21–44

    Article  CAS  PubMed  Google Scholar 

  36. Edwards DA, Nahai FR, Wright P . Pathways linking the olfactory bulbs with the medial preoptic anterior hypothalamus are important for intermale aggression in mice Physiol Behav 1993 53: 611–615

    Article  CAS  PubMed  Google Scholar 

  37. DaVanzo JP, Sydow M, Garris DR . Influence of isolation and training on fighting in mice with olfactory bulb lesions Physiol Behav 1983 31: 857–860

    Article  CAS  PubMed  Google Scholar 

  38. Newman SW . The medial extended amygdala in male reproductive behavior. A node in the mammalian social behavior network Ann NY Acad Sci 1999 877: 242–257

    Article  CAS  PubMed  Google Scholar 

  39. Meredith M . Vomeronasal, olfactory, hormonal convergence in the brain Cooperation or coincidence? Ann NY Acad Sci 1998 855: 349–361

    Article  CAS  PubMed  Google Scholar 

  40. Wood RI . Thinking about networks in the control of male hamster sexual behavior Horm Behav 1997 32: 40–45

    Article  CAS  PubMed  Google Scholar 

  41. Keverne EB . The vomeronasal organ Science 1999 286: 716–720

    Article  CAS  PubMed  Google Scholar 

  42. De Vries GJ, Buijs RM, Swaab DF . Ontogeny of the vasopressinergic neurons of the suprachiasmatic nucleus and their extrahypothalamic projections in the rat brain—presence of a sex difference in the lateral septum Brain Res 1981 218: 67–78

    Article  CAS  PubMed  Google Scholar 

  43. De Vries GJ, Miller MA . Anatomy and function of extrahypothalamic vasopressin systems in the brain Prog Brain Res 1998 119: 3–20

    Article  CAS  PubMed  Google Scholar 

  44. Buijs RM, De Vries GJ, Van Leeuwen FW, Swaab DF . Vasopressin and oxytocin: distribution and putative functions in the brain Prog Brain Res 1983 60: 115–122

    Article  CAS  PubMed  Google Scholar 

  45. Burbach JPH, Adan RA, Lolait SJ, Van Leeuwen FW, Mezey E, Palkovits M et al. Molecular neurobiology and pharmacology of the vasopressin/oxytocin receptor family Cell Mol Neurobiol 1995 15: 573–595

    Article  PubMed  Google Scholar 

  46. Ostrowski NL, Lolait SJ, Young WS III . Cellular localization of vasopressin V1a receptor messenger ribonucleic acid in adult male rat brain, pineal, and brain vasculature Endocrinology 1994 135: 1511–1528

    Article  CAS  PubMed  Google Scholar 

  47. Szot P, Bale TL, Dorsa DM . Distribution of messenger RNA for the vasopressin V1a receptor in the CNS of male and female rats Mol Brain Res 1994 24: 1–10

    Article  CAS  PubMed  Google Scholar 

  48. Everts HG, De Ruiter AJ, Koolhaas JM . Differential lateral septal vasopressin in wild-type rats: correlation with aggression Horm Behav 1997 31: 136–144

    Article  CAS  PubMed  Google Scholar 

  49. Stowers L, Holy TE, Meister M, Dulac C, Koentges G . Loss of sex discrimination and male-male aggression in mice deficient for TRP2 Science 2002 295: 1493–1500

    Article  CAS  PubMed  Google Scholar 

  50. Leypold BG, Yu CR, Leinders-Zufall T, Kim MM, Zufall F, Axel R . Altered sexual and social behaviors in trp2 mutant mice Proc Natl Acad Sci 2002 99: 6378–6381

    Article  Google Scholar 

  51. Ferguson JN, Young LJ, Hearn EF, Matzuk MM, Insel TR, Winslow JT . Social amnesion in mice lacking the oxytocin gene Nat Genet 2000 25: 284–288

    Article  CAS  PubMed  Google Scholar 

  52. Aguilera G, Rabadan-Diehl C . Vasopressinergic regulation of the hypothalamic-pituitary-adrenal axis: implications for stress adaptation Regul Pept 2000 96: 23–29

    Article  CAS  PubMed  Google Scholar 

  53. Ma XM, Levy A, Lightman SL . Emergence of an isolated arginine vasopressin (AVP) response to stress after repeated restraint: a study of both AVP and corticotropin-releasing hormone messenger ribonucleic acid (RNA) and heteronuclear RNA Endocrinology 1997 138: 4351–4357

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Jacki Crawley, Andrew Holmes, Jennifer Temple, GB Turgidson and Elka Skordalakes for helpful discussions and advice. We thank Joanna Sweigert for help with genotyping and various behavioral studies and, especially, Michael Brownstein and Howard Nash for critical reading of the manuscript. We also thank the animal care staff in Buildings 49 and 36 at NIH for honoring our numerous special requests. SJL and AMO'C were supported by the Welcome Trust.

Author information

Authors and Affiliations

  1. Section on Neural Gene Expression, NIMH, Bethesda, MD, USA

    S R Wersinger & W S Young III

  2. Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA, USA

    E I Ginns

  3. University Research Centre For Neuroendocrinology, University of Bristol, UK

    A-M O'Carroll & S J Lolait

Authors
  1. S R Wersinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E I Ginns
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A-M O'Carroll
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S J Lolait
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W S Young III
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to W S Young III.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wersinger, S., Ginns, E., O'Carroll, AM. et al. Vasopressin V1b receptor knockout reduces aggressive behavior in male mice. Mol Psychiatry 7, 975–984 (2002). https://doi.org/10.1038/sj.mp.4001195

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001195

Keywords

This article is cited by

Search

Advanced search

Quick links