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.

The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating, a behavior in which central dopamine (DA) has been implicated. Here, we used male prairie voles to examine the effects of drug exposure on pair bonding and related neural circuitry. In our first experiment, amphetamine (AMPH) motivated behavior was examined using a conditioned place preference (CPP) paradigm and was shown to be mediated by activation of D1-like DA receptors. Next, we examined the effects of repeated AMPH exposure on pair bonding. Intact and saline pretreated control males displayed mating-induced partner preferences, whereas males pretreated with AMPH at the doses effective to induce CPP failed to show mating-induced partner preferences. Such AMPH treatment also enhanced D1, but not D2, DA receptor expression in the nucleus accumbens (NAcc). Furthermore, pharmacological blockade of D1-like DA receptors in the NAcc rescued mating-induced partner preferences in AMPH-treated males. Together, our data indicate that repeated AMPH exposure may narrow the behavioral repertoire of male prairie voles via a DA receptor-specific mechanism in the NAcc, resulting in the impairment of pair bond formation.vole | CPP | D1 Receptor I t is widely accepted that motivated and emotional behaviors that promote fitness are regulated by brain reward circuitry including the mesolimbic dopamine (DA) system (1, 2). Although this system is often implicated in food intake and sexual behavior (3, 4), it has also been implicated in other naturally occurring motivated behaviors, such as social play between juveniles and social bonding between parent and offspring (5-9). Often underrepresented in research are the social bonds formed between adult mates, i.e., pair bonds. Recent investigation using a socially monogamous rodent species, the prairie vole (Microtus ochrogaster) (10-12), indicate that a great deal of the neural regulation underlying pair bond formation and maintenance occurs within the nucleus accumbens (NAcc) (13-15)-a mesolimbic brain region critical for mediating motivated behaviors (1, 2, 16).Although motivational circuitry evolved to promote fitness enhancing behavior such as feeding, mating, and social bonding (1, 17), it is vulnerable to artificial usurpation by drugs of abuse (8). For example, administration of psychostimulant drugs of abuse, such as cocaine and amphetamine (AMPH), results in persistent alterations of mesolimbic DA activity (18,19). The intense impact on this circuit by these and other addictive drugs has been suggested to decrease the perceived value of natural incentives (20), including those of a social nature (8). Although it is known that drug addicts show impaired social behavior (21), the neural regulation of interactions between drug experience and social attachment is poorly understood. This is because, in part, such interactions are difficult to model in traditional laboratory rodents that do not exhibit social bonding between adult conspecifics.The neurobiology of su...

The formation and maintenance of social bonds in adulthood is an essential component of human health. However studies investigating the underlying neurobiology of such behaviors have been scarce. Microtine rodents offer a unique comparative animal model to explore the neural processes responsible for pair bonding and its associated behaviors. Studies using monogamous prairie voles and other related species have recently offered insight into the neuroanatomical, neurobiological, and neurochemical underpinnings of social attachment. In this review, we will discuss the utility of the microtine rodents in comparative studies by exploring their natural history and social behavior in the laboratory. We will then summarize the data implicating vasopressin, oxytocin, and dopamine in the regulation of pair bonding. Finally, we will discuss the ways in which these neurochemical systems may interact to mediate this complex behavior.

Micronutrients include electrolytes, minerals, vitamins, and carotenoids, and are required in microgram or milligram quantities for cellular metabolism. The liver plays an important role in micronutrient metabolism and this metabolism often is altered in chronic liver diseases. Here, we review how the liver contributes to micronutrient metabolism; how impaired micronutrient metabolism may be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a systemic disorder of energy, glucose, and lipid homeostasis; and how insights gained from micronutrient biology have informed NAFLD therapeutics. Finally, we highlight some of the challenges and opportunities that remain with investigating the contribution of micronutrients to NAFLD pathology and suggest strategies to incorporate our understanding into the care of NAFLD patients.

Although the protective effects of social bonds on drug use/abuse have been well documented, we know little about the underlying neural mechanisms. Using the prairie vole (Microtus ochrogaster)—a socially monogamous rodent that forms long-term pair bonds after mating—we demonstrate that amphetamine (AMPH) conditioning induced a conditioned place preference (CPP) in sexually naïve (SN), but not pair-bonded (PB), males. Although AMPH treatment induced a similar magnitude of DA release in the nucleus accumbens (NAcc) of SN and PB males, it had differential effects on NAcc D1 receptor (D1R) binding. Specifically, AMPH treatment increased D1R binding in SN, but decreased D1R binding in PB males. NAcc D1R, but not D2R, antagonism blocked AMPH-induced CPP in SN males and NAcc D1R activation prior to AMPH conditioning enabled AMPH-induced CPP in PB males. Together, our data demonstrate that pair bonding experience decreases the rewarding properties of AMPH through a D1R mediated mechanism.