Histone deacetylase inhibitors facilitate partner preference formation in female prairie voles

In the socially monogamous prairie vole (Microtus ochrogaster), mating induces enduring pair-bonds initiated by partner preference formation and regulated by a variety of neurotransmitters including oxytocin, vasopressin, and dopamine. Here we examined potential epigenetic mechanisms mediating pair-bond regulation. We show that the histone deacetylase inhibitors sodium butyrate and TrichoStatin A (TSA) facilitate partner preference formation in female prairie voles in the absence of mating. This was associated with a specific up-regulation of oxytocin (OTR) and vasopressin V1a receptors (V1aR) in the nucleus accumbens, through an increase in histone acetylation at their respective promoter. Furthermore, TSA-facilitated partner preference was prevented by OTR or V1aR blockade in the nucleus accumbens. Importantly, mating-induced partner preference triggered the same epigenetic regulation of OTR and V1aR gene promoters as TSA. These observations thus indicate that TSA and mating facilitate partner preference through epigenetic events, providing the first direct evidence for an epigenetic regulation of pair-bonding.