Nonapeptide Receptor Research Articles

Distribution of Vasopressin 1a and Oxytocin Receptor Binding in the Basal Forebrain and Midbrain of Male and Female Mongolian Gerbils

The nonapeptide system modulates a diversity of social behaviors, including aggression, parental care, affiliation, sexual behavior, and pair bonding. Such social behaviors are regulated through oxytocin and vasopressin activation of the oxytocin receptor (OXTR) and vasopressin V1a receptor (AVPR1A) in the brain. Nonapeptide receptor distributions have been mapped for several species, however, studies have demonstrated that there is substantial variation across species. Mongolian gerbils (Meriones unguiculatus) are an excellent organism for studying family dynamics, social development, pair bonding, and territorial aggression. Although an increasing number of studies are examining the neural mechanisms of social behavior in Mongolian gerbils, nonapeptide receptor distributions have yet to be characterized for this species. Here we conducted receptor autoradiography to map distributions of OXTR and AVPR1A binding throughout the basal forebrain and midbrain of female and male Mongolian gerbils. Further, we assessed whether gonadal sex influenced binding densities in brain regions important for social behavior and reward, however, we observed no effects of sex on OXTR or AVPR1A binding densities. These findings provide mapping distributions of nonapeptide receptors in male and female Mongolian gerbils, laying a foundation for future studies that seek to manipulate the nonapeptide system to examine nonapeptide-mediated social behavior.

Distribution of vasopressin 1a and oxytocin receptor protein and mRNA in the basal forebrain and midbrain of the spiny mouse (Acomys cahirinus).

The nonapeptide system modulates numerous social behaviors through oxytocin and vasopressin activation of the oxytocin receptor (OXTR) and vasopressin receptor (AVPR1A) in the brain. OXTRs and AVPR1As are widely distributed throughout the brain and binding densities exhibit substantial variation within and across species. Although OXTR and AVPR1A binding distributions have been mapped for several rodents, this system has yet to be characterized in the spiny mouse (Acomys cahirinus). Here we conducted receptor autoradiography and in situ hybridization to map distributions of OXTR and AVPR1A binding and Oxtr and Avpr1a mRNA expression throughout the basal forebrain and midbrain of male and female spiny mice. We found that nonapeptide receptor mRNA is diffuse throughout the forebrain and midbrain and does not always align with OXTR and AVPR1A binding. Analyses of sex differences in brain regions involved in social behavior and reward revealed that males exhibit higher OXTR binding densities in the lateral septum, bed nucleus of the stria terminalis, and anterior hypothalamus. However, no association with gonadal sex was observed for AVPR1A binding. Hierarchical clustering analysis further revealed that co-expression patterns of OXTR and AVPR1A binding across brain regions involved in social behavior and reward differ between males and females. These findings provide mapping distributions and sex differences in nonapeptide receptors in spiny mice. Spiny mice are an excellent organism for studying grouping behaviors such as cooperation and prosociality, and the nonapeptide receptor mapping here can inform the study of nonapeptide-mediated behavior in a highly social, large group-living rodent.

Losing a parent in early-life impairs flock size discrimination and lowers oxytocin receptor abundance in a medial amygdala homologueof adult zebra finches.

Experiencing inadequate parental care during early-life diminishes adult social competencies. For example, low parental care impairs adult socio-cognitive abilities (e.g., recognizing familiar conspecifics) and affiliation (e.g., close social proximity); outcomes attributed to diminished medial amygdala nonapeptide functioning in rodents. Whether parental care has effects beyond familiarity, and if siblings have similar effects to parents, is unclear. Here, zebra finches were used to explore if parent and/or sibling number shape adult recognition and preference of small versus large flocks and nonapeptide (oxytocin, vasotocin) receptor expression in an avian homologue of the mammalian medial amygdala. Chicks were raised by single mothers or fathers in small broods or paired parents in small or large broods matched to single parents for chicks per nest or per parent, respectively. Pair-raised birds had preferred flock sizes as adults, but birds raised by single parents had equal preference for either size. Oxytocin receptor expression was lower in birds raised by single parents versus paired parents, but vasotocin receptor levels were unaffected. Such results highlight parents as formative antecedents of their offspring's social competencies related to group size preference and their nonapeptide mechanisms, outcomes that influence an animal's ability to live in social groups.

Expression profiles of genes encoding arginine vasotocin and isotocin receptors and the leucyl-cystinyl aminopeptidase (LNPEP) nonapeptide degradation enzyme in blue tilapia (Oreochromis aureus) during high salinity acclimation

ABSTRACT The nonapeptide hormone arginine vasotocin (VT) regulates osmotic balance in fishes by modulating ion and water transport. While VT’s osmoregulatory effects arise in part via changes in VT secretion, it remains uncertain which nonapeptide receptors mediate these effects, or whether adjustments in VT degradation also contribute. This study characterized gene transcript profiles for all known teleost nonapeptide receptors and for the VT and isotocin (IT) degradation enzyme leucyl-cystinyl aminopeptidase (lnpep) in the gill, kidney, and intestine – as well as transcriptional profiles for proVT and proIT mRNAs in hypothalamus and pituitary – of blue tilapia (Oreochromis aureus) during hyperosmotic challenge. Results presented here suggest that VT’s actions during salinity acclimation may be mediated by V1a-type receptor V1a2 in gill and intestine but multiple V2-type receptors in kidney, and provide evidence that lnpep expression is modulated concurrent with osmoregulation, possibly to alter local availability of nonapeptides as osmolality returns to homeostatic set points.

Subtypes of Neurohypophyseal Nonapeptide Receptors and Their Functions in Rat Kidneys.

The nonapeptides of neurohypophysis, vasotocin and mesotocin, detected in most vertebrates, are replaced by vasopressin and oxytocin in mammals. Using bioinformatics methods, we determined the spectrum of receptor subtypes for these hormones in mammals and their physiological effects in the kidneys of rats. A search for sequences similar to the vertebrate vasotocin receptor by proteomes and transcriptomas of nine mammalian species and the rat genome revealed three subtypes of vasopressin receptors (V1a, V1b, and V2) and one type of oxytocin receptors. In the kidneys of non-anesthetized rats, which received a water load of 2 ml per 100 g of body weight, three effects of vasopressin were revealed: 1) increased reabsorption of water and sodium, 2) increased excretion of potassium ions, and 3) increased excretion of sodium ions. It has been suggested that each of the effects on the kidney is associated with selective stimulation of the vasopressin receptor subtypes V2, V1b, and V1a depending on the concentration of nonapeptide. In experiments on non-anaesthetized rats with a water load, the injection of oxytocin reduces the reabsorption of solute-free water in the kidneys and increases the excretion of sodium ions. The possible physiological mechanisms behind the realization of both effects with the participation of a single type of oxytocin receptors are being analyzed. Thus, the spectrum of activated receptor subtypes varies depending on the current concentration of neurohypophyseal hormones, as a result of which the predominant effect on renal function changes, which ensures precise regulation of water-salt homeostasis.

Do nonapeptides regulate parental care depending on experience in zebra finches?

Recent research suggests that the nonapeptide neurohormones regulate parental behaviors in a diverse array of vertebrates. However, it remains unclear how these neurohormones regulate parental care among birds, especially those which exhibit biparental care, or whether hormonal effects are contingent on a bird's previous experience as a parent. We measured the effects of nonapeptides on parental behaviors by peripherally injecting, over three treatment days, a short-acting nonapeptide receptor antagonist (OTA) or a saline control into breeding pairs of zebra finches (Taeniopygia guttata) that either did or did not have previous parental experience. We then compared how the duration of parental behaviors changed over the five days of observation (including one day before and two days after injections were administered). To compare treatment effects on parental outcomes, we also measured chick growth and mortality rates for each pair. There was a nearly significant interaction between treatment and experience for the amount of time birds spent in the nest, with time in the nest declining across the experiment inexperienced and experienced OTA birds. There was also a significant treatment by trial day interaction for nest guarding and a treatment by experience by trial day interaction for nest maintenance. Chicks reared by parents that received the OTA had significantly lower growth rates than chicks reared by control parents and, among experienced birds, higher mortality relative to control birds. Together, these results provide some support for the hypothesis that nonapeptides play a role in regulating parental outcomes and some parental behaviors in both experienced and inexperienced zebra finches.

Evidence for a role of arginine vasotocin receptors in the gill during salinity acclimation by a euryhaline teleost fish.

The nonapeptide arginine vasotocin (AVT) regulates osmotic balance in teleost fishes, but its mechanisms of action are not fully understood. Recently, it was discovered that nonapeptide receptors in teleost fishes are differentiated into two V1a-type, several V2-type, and two isotocin (IT) receptors, but it remains unclear which receptors mediate AVT's effects on gill osmoregulation. Here, we examined the role of nonapeptide receptors in the gill of the euryhaline Amargosa pupfish (Cyprinodon nevadensis amargosae) during osmotic acclimation. Transcripts for the teleost V1a-type receptor v1a2 were upregulated over fourfold in gill 24 h after transferring pupfish from 7.5 ppt to seawater (35 ppt) or hypersaline (55 ppt) conditions and downregulated after transfer to freshwater (0.3 ppt). Gill transcripts for the nonapeptide degradation enzyme leucyl-cystinyl aminopeptidase (LNPEP) also increased in fish acclimating to 35 ppt. To test whether the effects of AVT on the gill might be mediated by a V1a-type receptor, we administered AVT or a V1-type receptor antagonist (Manning compound) intraperitoneally to pupfish before transfer to 0.4 ppt or 35 ppt. Pupfish transferred to 35 ppt exhibited elevated gill mRNA abundance for cystic fibrosis transmembrane conductance regulator (cftr), but that upregulation diminished under V1-receptor inhibition. AVT inhibited the increase in gill Na+/Cl- cotransporter 2 (ncc2) transcript abundance that occurs following transfer to hypoosmotic environments, whereas V1-type receptor antagonism increased ncc2 mRNAs even without a change in salinity. These findings indicate that AVT acts via a V1-type receptor to regulate gill Cl- transport by inhibiting Cl- uptake and facilitating Cl- secretion during seawater acclimation.

Tracking oxytocin functions in the rodent brain during the last 30 years: From push‐pull perfusion to chemogenetic silencing

A short overview is provided of the last 30 years of oxytocin (and vasopressin) research performed in our laboratories, starting with attempts to monitor the release of this nonapeptide in the rodent brain during physiological conditions such as suckling in the lactating animal. Using push-pull perfusion and microdialysis approaches, release patterns in hypothalamic and limbic brain regions could be characterised to occur from intact neuronal structures, to be independent of peripheral secretion into blood, and to respond differentially to various stimuli, particularly those related to reproduction and stress. Parallel efforts focused on the functional impact of central oxytocin release, including neuroendocrine and behavioural effects mediated by nonapeptide receptor interactions and subsequent intraneuronal signalling cascades. The use of a variety of sophisticated behavioural paradigms to manipulate central oxytocin release, along with pharmacological, genetic and pharmacogenetic approaches, revealed multiple consequences on social behaviours, particularly social fear.

Interactions of sex and early life social experiences at two developmental stages shape nonapeptide receptor profiles.

Early life social experiences are critical to behavioral and cognitive development, and can have a tremendous influence on developing social phenotypes. Most work has focused on outcomes of experiences at a single stage of development (e.g. perinatal or post-weaning). Few studies have assessed the impact of social experience at multiple developmental stages and across sex. Oxytocin and vasopressin are profoundly important for modulating social behavior and these nonapeptide systems are highly sensitive to developmental social experience, particularly in brain areas important for social behavior. We investigated whether oxytocin receptor (OTR) and vasopressin receptor (V1aR) distributions of prairie voles (Microtus ochrogaster) change as a function of parental composition within the natal nest or social composition after weaning. We raised pups either in the presence or absence of their fathers. At weaning, offspring were housed either individually or with a same-sex sibling. We also examined whether changes in receptor distributions are sexually dimorphic because the impact of the developmental environment on the nonapeptide system could be sex-dependent. We found that differences in nonapeptide receptor expression were region-specific, sex-specific and rearing condition-specific, indicating a high level of complexity in the ways that early life experiences shape the social brain. We found many more differences in V1aR density compared to OTR density, indicating that nonapeptide receptors demonstrate differential levels of neural plasticity and sensitivity to environmental and biological variables. Our data highlight that critical factors including biological sex and multiple experiences across the developmental continuum interact in complex ways to shape the social brain.

Nonapeptide Receptor Distributions in Promising Avian Models for the Neuroecology of Flocking.

Collective behaviors, including flocking and group vocalizing, are readily observable across a diversity of free-living avian populations, yet we know little about how neural and ecological factors interactively regulate these behaviors. Because of their involvement in mediating a variety of social behaviors, including avian flocking, nonapeptides are likely mediators of collective behaviors. To advance the neuroecological study of collective behaviors in birds, we sought to map the neuroanatomical distributions of nonapeptide receptors in three promising avian models that are found across a diversity of environments and widely ranging ecological conditions: European starlings, house sparrows, and rock doves. We performed receptor autoradiography using the commercially available nonapeptide receptor radioligands, 125I-ornithine vasotocin analog and 125I-linear vasopressin antagonist, on brain tissue sections from wild-caught individuals from each species. Because there is known pharmacological cross-reactivity between nonapeptide receptor subtypes, we also performed a novel, competitive-binding experiment to examine the composition of receptor populations. We detected binding in numerous regions throughout the brains of each species, with several similarities and differences worth noting. Specifically, we report that all three species exhibit binding in the lateral septum, a key brain area known to regulate avian flocking. In addition, sparrows and starlings show dense binding in the dorsal arcopallium, an area that has received scant attention in the study of social grouping. Furthermore, our competitive binding results suggest that receptor populations in sparrows and starlings differ in the lateral septum versus the dorsal arcopallium. By providing the first comprehensive maps of nonapeptide receptors in European starlings, house sparrows, and rock doves, our work supports the future use of these species as avian models for neuroecological studies of collective behaviors in wild birds.

Neural responses to familiar conspecifics are modulated by a nonapeptide receptor in a winter flocking sparrow

The social behavior network, a collection of reciprocally connected areas within the basal forebrain and midbrain, plays a conserved role in the regulation of vertebrate social behavior. Specific behaviors are associated with patterns of activity across the network, and these activity profiles vary with species and context. We investigated how the social behavior network responds to familiar social stimuli in a seasonally flocking songbird. Further, we explored how socially-induced neural responses are modulated by endogenous nonapeptide receptor blockade. Winter flocking dark-eyed juncos were exposed to either familiar conspecifics or a familiar empty aviary following a peripheral injection of either saline or [desGly-NH2,d(CH2)5, Tyr(Me)2,Thr4]-ornithine vasotocin, an VT3 receptor antagonist. Socially-exposed animals exhibited greater Fos induction across the social behavior network. Sex and drug effects were site-specific, with females tending to exhibit greater Fos responses to social stimuli and a greater sensitivity to VT3 antagonism. We suggest that in flocking animals, VT3 activation during social interaction may shift the pattern of neural activity towards the dorsocaudal lateral septum and rostral arcopallium and away from the extended amygdala, anterior and ventromedial hypothalamus, and the caudal ventral/ventrolateral lateral septum.

Effects of Chronic Oxytocin Administration and Diet Composition on Oxytocin and Vasopressin 1a Receptor Binding in the Rat Brain

Oxytocin (OT) elicits weight loss in diet-induced obese (DIO) rodents, nonhuman primates, and humans, in part, by reducing food intake. Chronic OT administration produces more sustained weight loss in high-fat diet (HFD)-fed DIO rodents relative to chow-fed controls, but the reasons for this effect remain unclear. We hypothesized that HFD-induced obesity is associated with elevated OT receptor (OXTR) binding in brain regions where OT is known to cause decreased food intake and that this sensitized neural system is one mechanism by which OT preferentially elicits weight loss in DIO rodents. We therefore determined the impact of diet (HFD vs chow) and drug treatment (chronic OT infusion vs vehicle) on (1) OXTR binding in hindbrain and forebrain sites where OT suppresses food intake relative to control sites that express OXTR and (2) forebrain vasopressin 1a receptor (AVPR1a) density to evaluate the specificity of any OT effects. Using quantitative receptor autoradiography, we found that (1) diet composition failed to alter OXTR or AVPR1a binding; (2) chronic OT treatment produced largely global reductions in forebrain OXTR and AVPR1a binding without significantly altering hindbrain OXTR binding. These findings suggest that forebrain OXTR and AVPR1a are down-regulated in response to chronic OT treatment. Given that chronic intranasal OT may be used as a therapeutic strategy to treat obesity, future studies should consider the potential downregulatory effect that chronic treatment can have across forebrain and hindbrain nonapeptide receptors and assess the potential contribution of both receptor subtypes to the outcome measures.

Dynamic expression of vasotocin and isotocin receptor genes in the marbled eel (Anguilla marmorata) following osmotic challenges

To examine the physiological roles of arginine vasotocin receptor (AVTR) and isotocin receptor (ITR) in osmoregulation of a euryhaline teleost, the marbled eel (Anguilla marmorata), three different genes coding for AVTRV1a2, AVTRV2 and ITR were cloned by screening an A. marmorata cDNA library. These receptors were expressed differentially and ubiquitously in the eight tissues we examined. The changes in mRNA expression levels of AVTRV1a2, AVTRV2, and ITR were assessed in a time-course study following salinity transfer from fresh water (FW, 0‰) to fresh water (FW, 0‰), brackish water (BW, 10‰) or saline water (SW, 25‰). When eels were transferred to BW, mRNA levels underwent an adaptive period, from 0 to 24 h, and a chronic regulatory period, starting at 24 h after transfer. In the adaptive period, the relative mRNA expression of AVTRV1a2, AVTRV2, and ITR increased in BW. But after this adaptive period, the mRNA levels of the three genes were significantly decreased compared to FW (control group, 0 h). The mRNA expression levels of AVTRV1a2, AVTRV2 and ITR were low in SW. The protein level of AVTRV1a2, a key protein in the brain, was also investigated and found to be consistent with mRNA results. Our results indicated that the nonapeptide receptor system may play a role in the acute stress response induced by hyper-osmotic challenge in marbled eels.

Developmental trajectories and influences of environmental complexity on oxytocin receptor and vasopressin 1A receptor expression in male and female prairie voles.

Nonapeptide receptors, like oxytocin receptor (OTR) and vasopressin 1a receptor (V1aR), modulate a variety of functions across taxa, and mediate phenotypic variation within and between species. Despite the popularity of studying nonapeptides in adults, developmental perspectives on properties of OTR and V1aR expression are lacking. Study of prairie voles (Microtus ochrogaster) has facilitated an understanding of mechanisms of social behavior and provides great potential to inform how early life experiences alter phenotype. We provide the first comprehensive profiling of OTR and V1aR in male and female prairie voles across postnatal development and into adulthood. Differences in receptor densities across the forebrain were region- and sex-specific. Postnatal changes in receptor expression fell into four themes: (a) constant over time, (b) increasing with age, (c) decreasing with age, or (d) peaking during late pre-weaning (postnatal day 15-21). We also examined the influence of post-weaning social and spatial enrichment (i.e., environmental complexity) on OTR and V1aR. Environmental complexity appeared to promote expression of OTR in males and females, and reduced expression of V1aR across several brain regions in males. Our results show that nonapeptide receptor profiles are plastic over development and suggest that different patterns of expression might represent functional differences in sensitivity to nonapeptide activation over a period when social environments are dynamic. Our results on environmental complexity suggest that nonapeptide sensitivity responds flexibly to different environmental contexts during development. Understanding the developmental trajectories of nonapeptide receptors provides a better understanding of the dynamic nature of social behavior and the underlying mechanisms.

Early life manipulations of vasopressin-family peptides alter vocal learning.

Vocal learning from social partners is crucial for the successful development of communication in a wide range of species. Social interactions organize attention and enhance motivation to learn species-typical behaviour. However, the neurobiological mechanisms connecting social motivation and vocal learning are unknown. Using zebra finches (Taeniopygia guttata), a ubiquitous model for vocal learning, we show that manipulations of nonapeptide hormones in the vasopressin family (arginine vasotocin, AVT) early in development can promote or disrupt both song and social motivation. Young male zebra finches, like human infants, are socially gregarious and require interactive feedback from adult tutors to learn mature vocal forms. To investigate the role of social motivational mechanisms in song learning, in two studies, we injected hatchling males with AVT or Manning compound (MC, a nonapeptide receptor antagonist) on days 2-8 post-hatching and recorded song at maturity. In both studies, MC males produced a worse match to tutor song than controls. In study 2, which experimentally controlled for tutor and genetic factors, AVT males also learned song significantly better compared with controls. Furthermore, song similarity correlated with several measures of social motivation throughout development. These findings provide the first evidence that nonapeptides are critical to the development of vocal learning.

Navigating Monogamy: Nonapeptide Sensitivity in a Memory Neural Circuit May Shape Social Behavior and Mating Decisions.

The role of memory in mating systems is often neglected despite the fact that most mating systems are defined in part by how animals use space. Monogamy, for example, is usually characterized by affiliative (e.g., pairbonding) and defensive (e.g., mate guarding) behaviors, but a high degree of spatial overlap in home range use is the easiest defining feature of monogamous animals in the wild. The nonapeptides vasopressin and oxytocin have been the focus of much attention for their importance in modulating social behavior, however this work has largely overshadowed their roles in learning and memory. To date, the understanding of memory systems and mechanisms governing social behavior have progressed relatively independently. Bridging these two areas will provide a deeper appreciation for understanding behavior, and in particular the mechanisms that mediate reproductive decision-making. Here, I argue that the ability to mate effectively as monogamous individuals is linked to the ability to track conspecifics in space. I discuss the connectivity across some well-known social and spatial memory nuclei, and propose that the nonapeptide receptors within these structures form a putative “socio-spatial memory neural circuit.” This purported circuit may function to integrate social and spatial information to shape mating decisions in a context-dependent fashion. The lateral septum and/or the nucleus accumbens, and neuromodulation therein, may act as an intermediary to relate socio-spatial information with social behavior. Identifying mechanisms responsible for relating information about the social world with mechanisms mediating mating tactics is crucial to fully appreciate the suite of factors driving reproductive decisions and social decision-making.

Pairing Increases Activation of V1aR, but not OTR, in Auditory Regions of Zebra Finches: The Importance of Signal Modality in Nonapeptide-Social Behavior Relationships.

Social relationships are complex, involving the production and comprehension of signals, individual recognition, and close coordination of behavior between two or more individuals. The nonapeptides oxytocin and vasopressin are widely believed to regulate social relationships. These findings come largely from prairie voles, in which nonapeptide receptors in olfactory neural circuits drive pair bonding. This research is assumed to apply to all species. Previous reviews have offered two competing hypotheses. The work of Sarah Newman has implicated a common neural network across species, the Social Behavior Network. In contrast, others have suggested that there are signal modality-specific networks that regulate social behavior. Our research focuses on evaluating these two competing hypotheses in the zebra finch, a species that relies heavily on vocal/auditory signals for communication, specifically the neural circuits underlying singing in males and song perception in females. We have demonstrated that the quality of vocal interactions is highly important for the formation of long-term monogamous bonds in zebra finches. Qualitative evidence at first suggests that nonapeptide receptor distributions are very different between monogamous rodents (olfactory species) and monogamous birds (vocal/auditory species). However, we have demonstrated that social bonding behaviors are not only correlated with activation of nonapeptide receptors in vocal and auditory circuits, but also involve regions of the common Social Behavior Network. Here, we show increased Vasopressin 1a receptor, but not oxytocin receptor, activation in two auditory regions following formation of a pair bond. To our knowledge, this is the first study to suggest a role of nonapeptides in the auditory circuit in pair bonding. Thus, we highlight converging mechanisms of social relationships and also point to the importance of studying multiple species to understand mechanisms of behavior.

Sex and pairing status explain variations in the activation of nonapeptide receptors in song and motivation regions.

The nonapeptides oxytocin and vasopressin have been implicated in a variety of social behaviors. In zebra finches, oxytocin antagonists decrease pairing in both sexes, and pairing, in turn, increases expression of both mesotocin (the avian homologue of oxytocin) and vasotocin (the avian homologue of vasopressin). Increases in mesotocin and vasotocin mRNA are correlated with the amount of directed singing by males. Thus, in the present study, we examined the hypothesis that activation of cells containing nonapeptide receptors in song-related regions (ventral tegmental area, lateral septum, and medial preoptic nucleus) would also be correlated with directed singing in males. To rule out the possibility that these regions are involved in general pairing motivation, we also included females as subjects. In the ventral tegmental area, males had higher ZENK and V1aR than females and paired animals (regardless of sex) had higher ZENK and V1aR than did unpaired animals. In the medial preoptic nucleus, paired animals had higher ZENK than did unpaired animals, and there were no sex or pairing effects in the lateral septum. Only ZENK + V1aR in the medial preoptic nucleus was correlated with singing in males. These findings suggest that pairing is associated activation of nonapeptide receptors in the ventral tegmental area and the medial preoptic nucleus, but there is only partial evidence that courtship singing accounts for these findings. (PsycINFO Database Record

Developmental effects of vasotocin and nonapeptide receptors on early social attachment and affiliative behavior in the zebra finch

Zebra finches demonstrate selective affiliation between juvenile offspring and parents, which, like affiliation between pair partners, is characterized by proximity, vocal communication and contact behaviors. This experiment tested the hypothesis that the nonapeptide arginine vasotocin (AVT, avian homologue of vasopressin) and nonapeptide receptors play a role prior to fledging in the development of affiliative behavior. Zebra finch hatchlings of both sexes received daily intracranial injections (post-hatch days 2–8) of either AVT, Manning Compound (MC, a potent V1a receptor antagonist) or saline (vehicle control). The social development of both sexes was assessed by measuring responsiveness to isolation from the family and subsequent reunion with the male parent after fledging. In addition, we assessed the changes in affiliation with the parents, unfamiliar males, and unfamiliar females each week throughout juvenile development. Compared to controls, MC subjects showed decreased attachment to the parents and MC males did not show the normal increase in affiliative interest in opposite sex individuals as they reached reproductive maturity. In contrast, AVT subjects showed a sustained affiliative interest in parents throughout development, and males showed increased interest in opposite sex conspecifics as they matured. These results provide the first evidence suggesting that AVT and nonapeptide receptors play organizational roles in social development in a bird.

Arginine Vasotocin, Isotocin and Nonapeptide Receptor Gene Expression Link to Social Status and Aggression in Sex‐Dependent Patterns

Nonapeptide hormones of the vasopressin/oxytocin family regulate social behaviours. In mammals and birds, variation in behaviour also is linked to expression patterns of the V1a-type receptor and the oxytocin/mesotocin receptor in the brain. Genome duplications, however, expand the diversity of nonapeptide receptors in actinopterygian fishes, and two distinct V1a-type receptors (v1a1 and v1a2) for vasotocin, as well as at least two V2-type receptors (v2a and v2b), have been identified in these taxa. The present study investigates how aggression connected to social status relates to the abundance patterns of gene transcripts encoding four vasotocin receptors, an isotocin receptor (itr), pro-vasotocin (proVT) and pro-isotocin (proIT) in the brain of the pupfish Cyprinodon nevadensis amargosae. Sexually-mature pupfish were maintained in mixed-sex social groups and assessed for individual variation in aggressive behaviours. Males in these groups behaved more aggressively than females, and larger fish exhibited higher aggression relative to smaller fish of the same sex. Hypothalamic proVT transcript abundance was elevated in dominant males compared to subordinate males, and correlated positively with individual variation in aggression in both social classes. Transcripts encoding vasotocin receptor v1a1 were at higher levels in the telencephalon and hypothalamus of socially subordinate males than dominant males. Dominant males exhibited elevated hypothalamic v1a2 receptor transcript abundance relative to subordinate males and females, and telencephalic v1a2 mRNA abundance in dominant males was also associated positively with individual aggressiveness. Transcripts in the telencephalon encoding itr were elevated in females relative to males, and both telencephalic proIT and hypothalamic itr transcript abundance varied with female social status. Taken together, these data link hypothalamic proVT expression to aggression and implicate forebrain expression of the V1a-type receptor v1a2 as potentially mediating the effects of vasotocin on behaviour in male fish. These findings also illustrate how associations between social status, aggression and gene expression within the VT and IT nonapeptide systems can be contingent on behavioural context.