Prairie voles (Microtus ochrogaster) are a socially monogamous species. Unlike other species of voles, they form long-lasting pair bonds with their partners. Studies comparing prairie voles to related species have revealed that oxytocin, vasopressin and dopamine signaling are necessary for the formation of partner preference. In males, partner preference requires vasopressin neurotransmission in the ventral pallidum and lateral septum, whereas oxytocin neurotransmission in the nucleus accumbens (NAc) and prelimbic cortex are essential in females. In both sexes, dopamine D2 receptors in the NAc facilitate the formation of partner preference, whereas dopamine D1 receptors inhibit pair-bonding. The long-lasting nature of pair bonds suggests that equally enduring molecular mechanisms may underlie their formation. On page 919, Wang and colleagues show that histone modifications are involved in modifying gene expression to promote formation of partner preference.

The authors observed that mating, which normally induces partner preference in female prairie voles, led to increased expression of the oxytocin receptor (OTR) and vasopressin receptor (V1aR) in NAc of females. This increase in expression was associated with an increase in histone 3 acetylation on lysine 14 (AcH3K14), a mark that is usually correlated with increased transcription, specifically at the oxtr and avpr1a promoters. If female voles were merely exposed to their prospective partners without mating, central administration of the histone deacetylase inhibitor trichostatin A (TSA) was sufficient to induce partner preference. Similar to mating, TSA infusion induced specific increases in AcH3K14 at the oxtr and avpr1a promoters and increased expression of OTR and V1aR in the NAc. Notably, infusion of OTR or V1aR antagonists into the brain blocked the ability of intra-NAc TSA to induce partner preference, indicating that these receptors are necessary for formation TSA-induced partner preference.

These results suggest that chromatin modifications underlie the formation of partner preference in prairie voles, adding to a growing list of behaviors that are regulated by such epigenetic mechanisms, which have previously been implicated in the formation of long-term memory, drug addiction and affective behaviors. Prairie voles, which exhibit more socially complex behaviors than many rodent species, have been championed as a model in which to study social affiliative behaviors more generally, and the hormones studied here, oxytocin and vasopressin, have been implicated in a wide range of social behaviors. These findings suggest that epigenetic mechanisms may also be involved in other social behaviors.