Zuoxin Wang

The neurobiology of pair bonding

A neurobiological model for pair-bond formation has emerged from studies in monogamous rodents. The neuropeptides oxytocin and vasopressin contribute to the processing of social cues necessary for individual recognition. Mesolimbic dopamine is involved in reinforcement and reward learning. Concurrent activation of neuropeptide and dopamine receptors in the reward centers of the brain during mating results in a conditioned partner preference, observed as a pair bond. Differential regulation of neuropeptide receptor expression may explain species differences in the ability to form pair bonds. These and other studies discussed here have intriguing implications for the neurobiology of social attachment in our own species.

Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene

The molecular mechanisms underlying the evolution of complex behaviour are poorly understood. The mammalian genus Microtus provides an excellent model for investigating the evolution of social behaviour. Prairie voles (Microtus ochrogaster) exhibit a monogamous social structure in nature, whereas closely related meadow voles (Microtus pennsylvanicus) are solitary and polygamous. In male prairie voles, both vasopressin and dopamine act in the ventral forebrain to regulate selective affiliation between adult mates, known as pair bond formation, as assessed by partner preference in the laboratory. The vasopressin V1a receptor (V1aR) is expressed at higher levels in the ventral forebrain of monogamous than in promiscuous vole species, whereas dopamine receptor distribution is relatively conserved between species. Here we substantially increase partner preference formation in the socially promiscuous meadow vole by using viral vector V1aR gene transfer into the ventral forebrain. We show that a change in the expression of a single gene in the larger context of pre-existing genetic and neural circuits can profoundly alter social behaviour, providing a potential molecular mechanism for the rapid evolution of complex social behaviour.

Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles

Although oxytocin (OT) and dopamine (DA) have been implicated in pair bond formation in monogamous prairie voles (Microtus ochrogaster), the nature of potential interactions between these two neurochemical systems and the brain circuits important for such interactions in the regulation of pair bonding have not been explored. Here, we demonstrated that access to both OT and DA D2-type receptors is necessary for pair bond formation, as blockade of either type of receptor prevented partner preferences induced by OT or a D2-type agonist. We also demonstrated that the nucleus accumbens (NAcc) is a brain area important for such OT-DA interactions. In NAcc, blockade of OT receptors prevented partner preferences induced by a D2-type agonist whereas blockade of D2-type, but not D1-type, DA receptors blocked OT-induced partner preferences. Together, our data suggest that concurrent activation of OT and DA D2-type receptors in NAcc is essential for pair bond formation in female prairie voles.

Nucleus accumbens dopamine differentially mediates the formation and maintenance of monogamous pair bonds

The involvement of dopamine within the nucleus accumbens in the formation and maintenance of pair bonds was assessed in a series of experiments using the monogamous prairie vole. We show that dopamine transmission that promotes pair bond formation occurs within the rostral shell of the nucleus accumbens, but not in its core or caudal shell. Within this specific brain region, D1- and D2-like receptor activation produced opposite effects: D1-like activation prevented pair bond formation, whereas D2-like activation facilitated it. After extended cohabitation with a female, male voles showed behavior indicative of pair bond maintenance—namely, selective aggression towards unfamiliar females. These voles also showed a significant upregulation in nucleus accumbens D1-like receptors, and blockade of these receptors abolished selective aggression. Thus, neuroplastic reorganization of the nucleus accumbens dopamine system is responsible for the enduring nature of monogamous pair bonding. Finally, we show that this system may also contribute to species-specific social organization.

Neuroendocrine bases of monogamy

A number of studies have implicated the neurohypophyseal peptides oxytocin and vasopressin in the central mediation of complex social behaviors, including affiliation, parental care and territorial aggression. Research on a monogamous rodent, the prairie vole (Microtus ochrogaster), suggests that these neuropeptides are also involved in the control of several behaviors associated with monogamy, including pair bonding, paternal care and mate guarding. Comparative studies using several species of vole have identified species-specific patterns of oxytocin- and vasopressin-receptor expression in the brain that appear to be associated with a monogamous versus non-monogamous social structure. Molecular studies suggest that changes in the regulation of oxytocin- and vasopressin-receptor gene expression underlie these species differences in receptor distribution and might provide a mechanism for the evolution of monogamy in voles.

Dopamine D2 Receptors in the Nucleus Accumbens Are Important for Social Attachment in Female Prairie Voles (Microtus ochrogaster)

The prairie vole (Microtus ochrogaster), a monogamous rodent that forms long-lasting pair bonds, has proven useful for the neurobiological study of social attachment. In the laboratory, pair bonds can be assessed by testing for a partner preference, a choice test in which pair-bonded voles regularly prefer their partner to a conspecific stranger. Studies reported here investigate the role of dopamine D2-like receptors (i.e., D2, D3, and D4 receptors) in the nucleus accumbens (NAcc) for the formation of a partner preference in female voles. Mating facilitated partner preference formation and associated with an approximately 50% increase in extracellular dopamine in the NAcc. Microinjection of the D2 antagonist eticlopride into the NAcc (but not the prelimbic cortex) blocked the formation of a partner preference in mating voles, whereas the D2 agonist quinpirole facilitated formation of a partner preference in the absence of mating. Taken together, these results suggest that D2-like receptors in the NAcc are important for the mediation of social attachments in female voles.

Vasopressin in the lateral septum regulates pair bond formation in male prairie voles (Microtus ochrogaster).

Male prairie voles (Microtus ochrogaster) form a pair bond with a female partner after mating, and this behavior is regulated by the neuropeptide vasopressin (AVP). The authors report that AVP in the lateral septum is important for pair bond formation. Administration of an AVP V1a receptor antagonist in the lateral septum blocked mating-induced pair bonding, whereas administration of AVP induced this behavior in the absence of mating. In addition, administration of an oxytocin (OT) receptor antagonist in the lateral septum also blocked pair bond formation induced by either mating or AVP administration, suggesting that the OT receptor blockade may have interfered with the AVP regulation of behavior. Together, these data provide evidence suggesting that AVP in the lateral septum regulates pair bond formation in male prairie voles and that this process requires access to both AVP and OT receptors.

The neurobiology of pair bonding: Insights from a socially monogamous rodent

The formation of enduring relationships between adult mates (i.e., pair bonds) is an integral aspect of human social behavior and has been implicated in both physical and psychological health. However, due to the inherent complexity of these bonds and the relative rarity with which they are formed in other mammalian species, we know surprisingly little about their underlying neurobiology. Over the past few decades, the prairie vole (Microtus ochrogaster) has emerged as an animal model of pair bonding. Research in this socially monogamous rodent has provided valuable insight into the neurobiological mechanisms that regulate pair bonding behaviors. Here, we review these studies and discuss the neural regulation of three behaviors inherent to pair bonding: the formation of partner preferences, the subsequent development of selective aggression toward unfamiliar conspecifics, and the bi-parental care of young. We focus on the role of vasopressin, oxytocin, and dopamine in the regulation of these behaviors, but also discuss the involvement of other neuropeptides, neurotransmitters, and hormones. These studies may not only contribute to the understanding of pair bonding in our own species, but may also offer insight into the underlying causes of social deficits noted in several mental health disorders.

Dopamine D2 Receptor-Mediated Regulation of Partner Preferences in Female Prairie Voles (Microtus ochrogaster}: A Mechanism for Pair Bonding?

This study examined the role of dopamine (DA) in partner preference (PP) formation in female prairie voles (Microtus ochrogaster). The nonspecific DA antagonist haloperidol blocked mating-induced PP, whereas the nonspecific DA agonist apomorphine induced PP without mating. The D2 antagonist eticlopride, but not the D1 antagonist SCH23390, blocked PP, whereas the D2 agonist quinpirole, but not the D1 agonist SKF38393, induced PP without mating. Injections of eticlopride before or immediately after mating, but not 24 hr after mating, impaired PP, indicating that DAs effects were not due to an interference with mating or sensory recognition. Finally, intracerebroventricular injections of eticlopride diminished PP. Together, these data suggest that mating-induced PP requires activation of D2 receptors and that social experience may activate dopaminergic pathways, with enduring effects on behavior.

Immunoreactivity of central vasopressin and oxytocin pathways in microtine rodents: a quantitative comparative study.

The genus Microtus includes several closely related species of voles with diverse patterns of social organization. Comparative studies of these species have previously tested hypotheses related to the evolution of monogamy and affiliation. In earlier studies, monogamous voles have been reported to differ from closely related nonmonogamous voles in the neural distribution of oxytocin and vasopressin receptors. These receptors have also been implicated in the behavioral differences relevant to monogamy, as oxytocin and vasopressin influence pair‐bond formation in the monogamous species. In the current study, two monogamous and two nonmonogamous vole species were compared for the distribution of oxytocin and vasopressin immunoreactivity. Contrary to our predictions, gender dimorphisms in vasopressin immunoreactivity were as evident in the monogamous as in the nonmonogamous species. Also, species differences in oxytocin and vasopressin staining were subtle relative to the profound species differences previously reported for receptor binding. These results are consistent with the hypothesis that neuroendocrine systems may evolve by changes in receptor distribution rather than by restructuring the presynaptic pathway.