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 insights 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.

After pair-bonding, male prairie voles (Microtus ochrogaster) display aggression toward novel females but not toward their female partner. Here we show that this selective aggression in pair-bonded male prairie voles is associated with increased release of vasopressin (AVP) in the anterior hypothalamus (AH). Pharmacological activation of AVP-V1a receptors (V1aR) in the AH induced selective aggression in sexually naive males, whereas V1aR blockade diminished selective aggression in pair-bonded males. Pair-bonded males also showed an increased density in V1aR binding in the AH compared to their sexually naive counterparts and overexpression of V1aR in the AH, by viral vector-mediated gene transfer, facilitated aggression toward novel females. These data demonstrate that AH-AVP is both necessary and sufficient in the regulation of selective aggression associated with pair-bonding. In the second part of this study, we examined the effects of amphetamine (AMPH) exposure on female-directed aggression and revealed the potential role of AH-AVP underlying this behavior. Repeated AMPH administration in sexually naive male prairie voles enhanced V1aR expression in the AH and induced aggression toward a familiar or unfamiliar female. In addition, this AMPH-induced aggression was blocked by intra-AH administration of a V1aR antagonist. Together, our data reveal a socioneurobiological mechanism, highlighting a critical role of AH-AVP in the regulation of aggression induced by pair-bonding or drug experience in socially monogamous male prairie voles.behavioral pharmacology ͉ drug abuse ͉ microdialysis ͉ neural plasticity ͉ viral-vector gene transfer A ggression is an agonistic behavior that plays an important role for survival and reproductive success. In both vertebrates (1) and invertebrates (2), aggression promotes fitness by acquiring territory, food, and mates, as well as by serving to protect offspring and avoid predation. In humans and nonhuman primates, aggressive behavior operates within social hierarchies to facilitate resource acquisition (3). Among the neurochemicals implicated in aggression (4, 5), arginine vasopressin (AVP), and its homolog vasotocin, have been found to regulate several forms of aggression in numerous species (6, 7) across diverse taxa (8, 9). Even in humans, central AVP correlates with aggressive behavior (10) and mediates anger (11). Therefore, the AVP system may have evolved to be primed by a wide variety of experiences to induce aggression, when appropriate, in social animals (12).Drug use can override neurobiological programs to activate maladaptive forms of agonistic behavior, engaging inappropriate types of physical aggression (13), such as domestic violence (14) and intimate partner homicide (15). As a result, chronic drug abuse can cause permanent neural reorganization (16,17), impairing the adaptive social brain (18), leading to the display of maladaptive social behavior (19). In rodent models such as hamsters, adolescent exposure to cocaine (20) or anabolic steroids (21, 22) induces ag...

Male prairie voles (Microtus ochrogaster) display mating-induced pair bonding indicated by social affiliation with their female partners and aggression toward unfamiliar conspecifics. In the present study, we characterized their aggression associated with pair bonding and examined the related neuronal activation and neurochemical architecture. Males that were pair-bonded for 2 weeks displayed intense levels of aggression toward a female or male conspecific stranger but maintained a high level of social affiliation with their familiar female partners. These social interactions induced increases in neural activation, indicated by increased density of Fos-immunoreactive staining (Fos-ir) in several brain regions including the bed nucleus of the stria terminalis (BNST), medial preoptic area (MPOA), paraventricular nucleus (PVN), anterior cortical (AcA), and medial nuclei (MeA) of the amygdala. In the anterior hypothalamus (AH), increased density of Fos-ir staining was found specifically to be associated with aggression toward unfamiliar female or male strangers. In addition, higher densities of AH cells that were stained for tyrosine hydroxylase (TH) or vasopressin (AVP) were also labeled with Fos-ir in these males displaying aggression toward a conspecific stranger compared with males displaying social affiliation toward their female partner. Together, our results indicate that dopamine and vasopressin in the AH may be involved in the regulation of enduring aggression associated with pair bonding in male prairie voles.

Findings suggest that lower levels of prenatal testosterone exposure and higher adult levels of estradiol are associated with increased eating disorder symptoms. We hypothesize that the relatively low level of testosterone before birth in females permits their brains to respond to estrogens at puberty, when the hormones activate the genes contributing to disordered eating in vulnerable girls.

Gonadal hormones may exert permanent organizational effects on sexually dimorphic finger-length ratios and sexually dimorphic behavior expressed in childhood attention deficit-hyperactivity disorder (ADHD). This study extended recent work examining associations between finger-length ratios (specifically, 2D:4D) and ADHD in a well-characterized, clinically diagnosed, communityrecruited sample of boys and girls. A multistage, diagnostic procedure was utilized to identify 113 children with ADHD and 137 non-ADHD comparison children. Right-hand digit ratios showed significant mean differences by gender, as well as associations with ADHD diagnosis. Boys with ADHD had more masculinized digit ratios than control-group boys. More masculine right 2D:4D and 3D:4D ratios were correlated with parent-and teacher-rated inattentive and hyperactiveimpulsive symptoms in boys but not in girls. Masculinized finger-length ratios were associated with hyperactive-impulsive and oppositional-defiant symptoms, but associations were largest with symptoms of inattention. It is concluded that prenatal, organizational effects of gonadal hormones may play a role in the development of ADHD and contribute to explaining sex differences in the prevalence rates of this childhood disorder. Keywordstestosterone; finger-length ratio; 2D:4D; ADHD; sex differences Males are more vulnerable than females to developing a range of learning and behavioral disorders during childhood. Attention deficit-hyperactivity disorder (ADHD) is one of the most common and impairing sexually dimorphic clinical psychopathologies, with boys about three times more likely to be identified with ADHD than girls in population samples (American Psychiatric Association, 2000;Pastor & Reuben, 2002;Wolraich, Hannah, Baumgaertel, & Feurer, 1998). In addition, there may be sex differences in the correlates of the disorder. Although boys with ADHD appear to be more inattentive and hyperactive-impulsive than girls with the disorder, particularly in school (Gaub & Carlson, 1997;Gershon, 2002;Hartung et al., 2002), girls with ADHD may have worse cognitive impairment than boys with the disorder (Biederman et al., 1999;Gaub & Carlson, 1997;Newcorn et al., 2001). The precise neurobiological mechanisms underlying sex differences in the prevalence rates of developmental learning and behavioral disorders are complex and underresearched.The male sex bias in ADHD and its precursor behaviors is apparent during early preschool years (Hart, Lahey, Loeber, Applegate, & Frick, 1995), a period marked by rapid neural organization (Breedlove & Hampson, 2002). Males are typically exposed to testosterone perinatally, whereas females develop in the relative absence of testosterone (Morris, Jordan, & Breedlove, 2004). This differential exposure to steroid hormones produces specific malelike and/or female-like brain-behavior patterns . Therefore, these prenatal events may be related to sex differences in prevalence rates of ADHD. However, research on hormonal effects in ADHD is sparse, despite conse...