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