The present study examines the developmental consequences of neonatal exposure to oxytocin on adult social behaviors in female prairie voles (Microtus ochrogaster). Female neonates were injected within 24 hours of birth with isotonic saline or one of four dosages of oxytocin (OT). As adults, females were tested in an elevated plus-maze paradigm (a measure of anxiety and exploratory behavior), and for alloparental behavior and partner preferences. At 2 mg/kg OT, females took longer to approach pups, but were the only group to form a statistically significant within-group partner preference. At 4 mg/kg OT, females retrieved pups significantly more frequently but no longer displayed a partner preference; while females treated developmentally with 8 mg/kg spent significantly more time in side-to-side contact with a male stranger than any other treatment group. OT may have broad developmental consequences, but these effects are not linear and may both increase and decrease the propensity to display behaviors such as pair-bonding.The neuropeptide oxytocin (OT) has been implicated in social behavior in both male and female mammals. OT's peripheral effects include the induction of parturition and milk let-down, while central OT has been associated with the onset of maternal behavior (Pedersen and Prange Jr., 1979;Pedersen et al., 1982;Pedersen and Boccia, 2002), and other positive social behaviors such as pair-bonding (Insel and Hulihan, 1995;Carter and Altemus, 1997;Cho et al., 1999) and male parental care (Bales et al., 2004b). It is also becoming evident that manipulations of OT and a related peptide, arginine vasopressin (AVP) during the perinatal period of life can have life-long implications for social behavior and neuroendocrine function (Stribley and Carter, 1999;Diaz-Cabiale et al., 2000;Carter, 2003;Lipschitz et al., 2003). These exposures can be either endogenous, through responses to touch, warmth (Uvnas-Moberg, 1998) or perhaps through OT in breast milk (Leake et al., 1981); they could also be pharmacological, for example through use of pitocin or an oxytocin antagonist to manipulate labor (Husslein, 2002).In this context, we have begun to examine the consequences of OT manipulations in early life for subsequent social behaviors and neuroendocrine variables. Because we were particularly interested in the developmental control of social behaviors such as pair-bond formation and biparental behaviors, we chose to study the socially monogamous prairie vole (Microtus ochrogaster). In this species both males and females display parental care and form selective partner preferences indicative of pair-bonding, although the mechanisms for these behaviors Please direct correspondence to: Karen L. Bales, Dept. of Psychology, One Shields Ave., University of California, Davis, CA 95616. Ph: (530) 754−5890, Fax: (530) 752−2087, email: klbales@ucdavis.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this e...

The direct costs of paternal care are relatively well documented in primates, however little research has explored these effects in monogamous rodents. The present study examines the long-term effects that pairing and parenting have on male prairie voles. We hypothesized that there would be a significant weight loss over the course of pairing and parenting, presumably from the energetic demands that accompany these changes in social condition. In a longitudinal study, we followed ten male prairie voles through being housed with their brother; paired with a female; and caring for three consecutive litters. We found a significant drop in bodyweight across time, with maximum weight loss near the weaning of the first litter. At that same time, feeding increased, leading to possible recovery in weight; however, leptin levels dropped precipitously across time and did not recover. Corticosterone did not change significantly across time points, and overall activity levels also did not vary significantly over the course of the study. In addition, newly paired males showed a significant increase in preference for a 2% sucrose solution during a three-hour test, indicating a metabolic need for more calories. A cross-sectional study confirmed leptin and corticosterone findings, and showed significant loss of subcutaneous (inguinal) fat in males that had cared for a litter of pups, when compared to males housed with their brothers or newly paired males. These results suggest that cohabitation with a female, and caring for pups, all have costs for male prairie voles.

The vast majority of animals mate more or less promiscuously. A few mammals, including humans, utilize more restrained mating strategies that entail a longer term affiliation with a single mating partner. Such pair bonding mating strategies have been resistant to genetic analysis because of a lack of suitable model organisms. Prairie voles are small mouse-like rodents that form enduring pair bonds in the wild as well as in the laboratory, and consequently they have been used widely to study social bonding behavior. The lack of targeted genetic approaches in this species however has restricted the study of the molecular and neural circuit basis of pair bonds. As a first step in rendering the prairie vole amenable to reverse genetics, we have generated induced pluripotent stem cell (IPSC) lines from prairie vole fibroblasts using retroviral transduction of reprogramming factors. These IPSC lines display the cellular and molecular hallmarks of IPSC cells from other organisms, including mice and humans. Moreover, the prairie vole IPSC lines have pluripotent differentiation potential since they can give rise to all three germ layers in tissue culture and in vivo. These IPSC lines can now be used to develop conditions that facilitate homologous recombination and eventually the generation of prairie voles bearing targeted genetic modifications to study the molecular and neural basis of pair bond formation.

The transition to parenthood is generally associated with a reduction in anxiety or anxiety-like behavior across a wide range of species. In some species, juveniles provide supplementary parental care for younger siblings, a behavior known as alloparenting. Although the fitness consequences of alloparenting behavior have been a focus of evolutionary research, less is known about how alloparenting behavior impacts affective states. In the socially monogamous prairie vole (Microtus ochrogaster), most juveniles exhibit alloparenting behavior, making the species an ideal model for examining the effects of alloparenting on future behavioral outcomes. We randomly assigned juvenile voles to alloparenting (AL) or no alloparenting (NoAL) groups and behaviorally phenotyped them for anxiety-like and social behaviors using the elevated plus maze (EPM), open field test (OFT), startle box, social interaction test, juvenile affiliation test, and partner preference test. AL voles displayed more anxiety-like and less exploratory behavior than NoAL voles, spending significantly less time in the open arms of the EPM and center of an open field. We dissected the CA1 region of the hippocampus and the bed nucleus of the stria terminalis (BNST) from brains of behaviorally phenotyped voles and nontested siblings as well. Decreased BDNF expression in CA1 has generally been associated with increased anxiety-like behavior in other rodents, while an anxiogenic role for BDNF in BNST is less established. Western blot analyses showed that alloparenting experience increased expression of brain derived neurotrophic factor (BDNF) in the bed nucleus of stria terminalis (BNST) but decreased BDNF expression in the CA1 region of hippocampus (CA1) of nontested voles. There were similar differences in BNST BDNF of behaviorally phenotyped voles, and BDNF levels within this region were negatively correlated with exploratory behavior (i.e. time in center of OFT). Our results suggest that BDNF signaling in BNST and CA1 fluctuate with alloparenting experience, and they contribute to an increasingly complex “BDNF hypothesis” in which behavioral effects of this molecule are region-specific.