Elsevier

Hormones and Behavior

Volume 61, Issue 3, March 2012, Pages 293-303
Hormones and Behavior

Review
Both oxytocin and vasopressin are mediators of maternal care and aggression in rodents: From central release to sites of action

https://doi.org/10.1016/j.yhbeh.2011.11.002Get rights and content

Abstract

In the mammalian peripartum period, the activity of both the brain oxytocin and vasopressin system is elevated as part of the physiological adaptations occurring in the mother. This is reflected by increased expression and intracerebral release of oxytocin and vasopressin, as well as increased neuropeptide receptor expression and binding.

In this review we discuss the functional role of the brain oxytocin and vasopressin system in the context of maternal behavior, specifically maternal care and maternal aggression in rodents. In order to enable the identification of significant and peptide-specific contributions to the display of maternal behavior, various complementary animal models of maternal care and/or maternal aggression were studied, including rats selectively bred for differences in anxiety-related behavior (HAB and LAB dams), monitoring of local neuropeptide release during ongoing maternal behavior, and local pharmacological or genetic manipulations of the neuropeptide systems. The medial preoptic area was identified as a major site for oxytocin- and vasopressin-mediated maternal care. Furthermore, both oxytocin and vasopressin release and receptor activation in the central amygdala and the bed nucleus of the stria terminalis play an important role for maternal aggression.

This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

Highlights

► Brain OXT and AVP systems are activated peripartum. ► Review of their functional role in maternal care and aggression. ► Summary of central release patterns of OXT and AVP during mother–infant interaction. ► Behavioral changes following specific manipulations of these systems.

Introduction

Social behavior is considered to be any behavior caused by, or affecting, another individual, usually of the same species (as introduced in 1969 by the U.S. National Library of Medicine's controlled vocabulary). The intra-species specific display and perception of social behavior is an important prerequisite for living in and benefiting from a complex social environment. Social behavior such as communication, affiliation, social cognition, aggression, and reproduction has evolved based on highly conserved adaptations in brain morphology, neuronal connectivity and neurochemistry (Insel and Young, 2000). For example, most of these behaviors are modulated by neuropeptides, such as those from the oxytocin (OXT) / vasopressin (AVP) family of nonapeptides. In contrast to classical, e.g. monoaminergic and amino acid neurotransmitters, neuropeptides have a rather flexible mode of action: They can be released from all parts of the neuronal membrane within a particular brain region and can exert both short and more distant as well as rapid and prolonged intracerebral actions. Also, these neuropeptide systems show a high degree of plasticity as their activity can be altered by physiological or environmental stimuli. For example, in the mammalian peripartum period the activity of both brain OXT and AVP is highly elevated as a result of substantial physiological, in particular hormonal, adaptations, but also of sensory stimuli arising from the offspring (for review see: Slattery and Neumann, 2008, Neumann, 2003, Walker et al., 2001, Numan and Insel, 2003). This is reflected by an increase in gene expression of the neuropeptide and its receptor, intracerebral release, as well as neuropeptide receptor binding.

Members of the OXT / AVP family modulate various aspects of social, in particular reproductive, behavior not only in mammalian and vertebrate species, but also in invertebrates, although structural differences between the ancestral nonapeptides and mammalian OXT/AVP exist (Acher and Chauvet, 1995). For example, conopressin, annetocin, and vacotocin, members of the nonapeptide family in snails, earth-worms, and fish, respectively, modulate female egg laying behavior in those species. Also, mesotocin promotes birth and the mother's body posture necessary for the newborn Australian marsupial crawling into the mother's pouch (Bathgate et al., 1995). Based on these findings from various species, including laboratory rodents, the involvement of brain OXT and AVP in maternal care and aggression underlie the evolutionary conservation of their role in female reproduction.

While we will focus on the brain OXT and AVP systems here, it needs to be mentioned that other neurotransmitter systems are also involved in regulating maternal care and aggression, partly also via actions on the OXT and/or AVP system. Amongst these are prolactin (Mann and Bridges, 2001), dopamine (Numan and Insel, 2003), sex steroids like estrogen and progesterone (Brunton and Russell, 2010), or corticotropin-releasing factor (CRF) (D'Anna and Gammie, 2009, Gammie et al., 2004).

Section snippets

Maternal behavior of the lactating mother: care and defensive aggression

Maternal behavior is probably the most important social behavior in female mammals, providing nutrition, warmth, protection, and close social stimuli for the offspring. The term “maternal behavior” describes two distinct complexes of behaviors, i.e. maternal care and maternal aggression, which reflect any offspring-directed behavior and their defense against a potential threat, respectively. In order to become maternal, the mother's brain undergoes various physiological changes to meet the

Animal models of maternal behavior

The complexity of maternal behavior provides numerous areas for ethological research, such as the care and defense of the offspring, the rewarding nature of these behaviors, and the long-lasting mother–infant bond. To reveal the detailed neuronal and biochemical mechanisms of naturally occurring maternal behavior is of general heuristic value, and appropriate animal models were used over the years including sheep (for review see (Dwyer, 2008, Kendrick et al., 1997, Keverne and Kendrick, 1994)),

OXT as a regulator of maternal behavior

OXT as a neurohormone in the periphery is critical for reproductive functions peripartum, i.e. promotion of labor and milk ejection. Simultaneously, OXT is also released within various brain regions including the paraventricular nucleus (PVN), supraoptic nucleus (SON), septum, hippocampus, and olfactory bulb (OB) (Kendrick et al., 1988, Landgraf et al., 1991, Moos et al., 1991, Moos et al., 1989, Neumann and Landgraf, 1989, Neumann et al., 1993a, Neumann et al., 1993b). Within the hypothalamus,

AVP as a regulator of maternal behavior

In contrast to OXT, most of the research on AVP as a modulator of mammalian social behavior has focused on males (Caldwell et al., 2008, Veenema and Neumann, 2008). Consequently, gender-specific social functions of the AVP—and OXT—systems have been postulated (Donaldson and Young, 2008, Insel and Young, 2001). So far, AVP has been described to regulate, for example, social recognition and social interaction in males (Bielsky and Young, 2004, Engelmann et al., 1994, Ferguson et al., 2002,

Conclusions

Over the past years we and others have substantially increased our understanding of the neuropeptidergic regulation of maternal behavior using various animal models of maternal behavior and complementary experimental techniques. Both, the brain OXT and AVP systems are importantly involved in the fine-tuned regulation of maternal care and aggression: Whereas the brain OXT system is essential for the onset of maternal care at parturition, the maintenance of ongoing maternal behavior is also

Acknowledgments

The authors are grateful to D. Beiderbeck for the coordination of the HAB/LAB breeding throughout many studies, to J. Hönig for her support conducting the MPOA/OXT-A study, R. Landgraf for the continuous performance of the radioimmunoassay, and to M. Manning for the continuous supply with nonapeptide antagonists.

References (160)

  • A.R. Consiglio et al.

    Lesion of hypothalamic paraventricular nucleus and maternal aggressive behavior in female rats

    Physiol. Behav.

    (1996)
  • K.L. D'Anna et al.

    Maternal profiling of corticotropin-releasing factor receptor 2 deficient mice in association with restraint stress

    Brain Res.

    (2008)
  • G.J. De Vries et al.

    Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints

    Neuroscience

    (2006)
  • M. Engelmann et al.

    Effects of Morris water maze testing on the neuroendocrine stress response and intrahypothalamic release of vasopressin and oxytocin in the rat

    Horm. Behav.

    (2006)
  • M.S. Erskine et al.

    Intraspecific fighting during late pregnancy and lactation in rats and effects of litter removal

    Behav. Biol.

    (1978)
  • M.S. Erskine et al.

    Aggression in the lactating rat: effects of intruder age and test arena

    Behav. Biol.

    (1978)
  • J.N. Ferguson et al.

    The neuroendocrine basis of social recognition

    Front. Neuroendocrinol.

    (2002)
  • O. Gaffori et al.

    Disruption of maternal behavior and appearance of cannibalism after ventral mesencephalic tegmentum lesions

    Physiol. Behav.

    (1979)
  • S.C. Gammie et al.

    Neurotensin inversely modulates maternal aggression

    Neuroscience

    (2009)
  • S.C. Gammie et al.

    cFOS and pCREB activation and maternal aggression in mice

    Brain Res.

    (2001)
  • S.C. Gammie et al.

    Deletion of corticotropin-releasing factor binding protein selectively impairs maternal, but not intermale aggression

    Neuroscience

    (2008)
  • M. Giovenardi et al.

    Hypothalamic paraventricular nucleus modulates maternal aggression in rats: effects of ibotenic acid lesion and oxytocin antisense

    Physiol. Behav.

    (1998)
  • J.L. Goodson

    Nonapeptides and the evolutionary patterning of sociality

    Prog. Brain Res.

    (2008)
  • N.S. Hasen et al.

    Differential fos activation in virgin and lactating mice in response to an intruder

    Physiol. Behav.

    (2005)
  • N.S. Hasen et al.

    Maternal aggression: new insights from Egr-1

    Brain Res.

    (2006)
  • G.I. Hatton et al.

    Neural mechanisms underlying the milk ejection burst and reflex

    Prog. Brain Res.

    (2008)
  • T.R. Insel et al.

    Lesions of the hypothalamic paraventricular nucleus disrupt the initiation of maternal behavior

    Physiol. Behav.

    (1989)
  • T.R. Insel et al.

    Neuropeptides and the evolution of social behavior

    Curr. Opin. Neurobiol.

    (2000)
  • A.S. Ivy et al.

    Dysfunctional nurturing behavior in rat dams with limited access to nesting material: a clinically relevant model for early-life stress

    Neuroscience

    (2008)
  • M.E. Keck et al.

    Vasopressin mediates the response of the combined dexamethasone/CRH test in hyper-anxious rats: implications for pathogenesis of affective disorders

    Neuropsychopharmacology

    (2002)
  • K.M. Kendrick et al.

    Neural control of maternal behaviour and olfactory recognition of offspring

    Brain Res. Bull.

    (1997)
  • K.M. Kendrick et al.

    Intracranial dialysis measurement of oxytocin, monoamine and uric acid release from the olfactory bulb and substantia nigra of sheep during parturition, suckling, separation from lambs and eating

    Brain Res.

    (1988)
  • R. Landgraf et al.

    Candidate genes of anxiety-related behavior in HAB/LAB rats and mice: focus on vasopressin and glyoxalase-I

    Neurosci. Biobehav. Rev.

    (2007)
  • R. Landgraf et al.

    Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication

    Front. Neuroendocrinol.

    (2004)
  • J. LeDoux

    The amygdala

    Curr. Biol.

    (2007)
  • F. Levy et al.

    Oxytocin and vasopressin release in the olfactory bulb of parturient ewes: changes with maternal experience and effects on acetylcholine, gamma-aminobutyric acid, glutamate and noradrenaline release

    Brain Res.

    (1995)
  • S.L. Lightman et al.

    Peripartum plasticity within the hypothalamo-pituitary-adrenal axis

    Prog. Brain Res.

    (2001)
  • J.S. Lonstein

    Regulation of anxiety during the postpartum period

    Front. Neuroendocrinol.

    (2007)
  • J.S. Lonstein et al.

    Sensory, hormonal, and neural control of maternal aggression in laboratory rodents

    Neurosci. Biobehav. Rev.

    (2002)
  • S.M. Luckman

    Fos expression within regions of the preoptic area, hypothalamus and brainstem during pregnancy and parturition

    Brain Res.

    (1995)
  • P.E. Mann et al.

    Lactogenic hormone regulation of maternal behavior

    Prog. Brain Res.

    (2001)
  • L.R. Meek et al.

    Effects of stress during pregnancy on maternal behavior in mice

    Physiol. Behav.

    (2001)
  • B.C. Nephew et al.

    Arginine vasopressin V1a receptor antagonist impairs maternal memory in rats

    Physiol. Behav.

    (2008)
  • B.C. Nephew et al.

    Central actions of arginine vasopressin and a V1a receptor antagonist on maternal aggression, maternal behavior, and grooming in lactating rats

    Pharmacol. Biochem. Behav.

    (2008)
  • B.C. Nephew et al.

    Vasopressin mediates enhanced offspring protection in multiparous rats

    Neuropharmacology

    (2010)
  • R.A. Bathgate et al.

    Comparative aspects of oxytocin-like hormones in marsupials

    Adv. Exp. Med. Biol.

    (1995)
  • S.L. Bealer et al.

    Oxytocin receptor binding in the hypothalamus during gestation in rats

    Am. J. Physiol. Regul. Integr. Comp. Physiol.

    (2006)
  • I.F. Bielsky et al.

    Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice

    Neuropsychopharmacology

    (2004)
  • O.J. Bosch et al.

    Brain oxytocin correlates with maternal aggression: link to anxiety

    J. Neurosci.

    (2005)
  • O.J. Bosch et al.

    Brain vasopressin regulates maternal behavior and aggression

  • Cited by (312)

    View all citing articles on Scopus
    View full text