Neural mechanisms underlying pair bond formation in vole species

Vole species are a useful animal model for the study of the neurobiology underlying social attachment behavior because of their great diversity in social organization. Comparative studies can be conducted on the monogamous prairie vole (Microtus ochrogaster) and the promiscuous meadow (Microtus pennsylvanicus) voles to elucidate the neural mechanisms underlying pair bond formation between adult mates. The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) modulate pair bond formation in prairie voles. Considerable species differences exist in the oxytocin and vasopressin V1a receptor (OTR and V1aR, respectively) brain distribution patterns between monogamous and promiscuous species.; In this dissertation, the specific brain regions expressing OTR and V1aR are identified in the ventral forebrain of the prairie vole. These brain regions, including the nucleus accumbens and the ventral pallidum, are critically involved in the mesolimbic dopamine reward circuits. Using the immediate-early gene product Fos as a marker of neural activation, these brain regions are shown to be activated during the initial steps of pair bond formation in male prairie voles. Infusion of a selective V1aR antagonist into the ventral pallidum prevented partner preference formation in male prairie voles. These results are consistent with the hypothesis that reward mechanisms are engaged to initiate and maintain pair bond formation in prairie voles. The final experiment examines the role of V1aR in the ventral pallidum of the promiscuous meadow vole. Meadow voles express relatively few V1aR in the ventral pallidum compared to prairie voles, and we hypothesized that monogamous behavior would be conferred by the presence of V1aR in the ventral pallidum. To directly test this hypothesis, viral vector-mediated gene transfer was used to over-express V1aR in the ventral pallidum of male meadow voles. Transgenic meadow voles formed pair bonds with their mates, and like prairie voles, these pair bonds were dependent upon dopamine neurotransmission, suggesting the use of similar underlying reward mechanisms. Taken together, these experiments conclusively demonstrate that V1aR activation in the ventral pallidum is both necessary and sufficient for pair bond formation across vole species. These data also provide insight into the neural mechanisms underlying social attachment.