Histone deacetylase inhibitors facilitate partner preference formation in female prairie voles


In the socially monogamous prairie vole (Microtus ochrogaster), mating induces enduring pair-bonds that are initiated by partner preference formation and regulated by a variety of neurotransmitters, including oxytocin, vasopressin and dopamine. We examined potential epigenetic mechanisms mediating pair-bond regulation and found that the histone deacetylase inhibitors sodium butyrate and trichostatin A (TSA) facilitated partner preference formation in female prairie voles in the absence of mating. This was associated with a specific upregulation of oxytocin receptor (OTR, oxtr) and vasopressin V1a receptor (V1aR, avpr1a) in the nucleus accumbens (NAcc), through an increase in histone acetylation at their respective promoters. Furthermore, TSA-facilitated partner preference was prevented by OTR or V1aR blockade in the NAcc. Notably, mating-induced partner preference triggered the same epigenetic regulation of oxtr and avpr1a gene promoters as TSA. These observations indicate that TSA and mating facilitate partner preference through epigenetic events, providing, to the best of our knowledge, the first direct evidence for epigenetic regulation of pair-bonding.

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Figure 1: An acute injection of TSA facilitates partner preference formation in female prairie voles in the absence of mating.
Figure 2: TSA treatment (0.4 ng) upregulates OTR and V1aR in female prairie voles during cohabitation with a male in the absence of mating.
Figure 3: TSA treatment enhances histone acetylation of oxtr and avpr1a promoters during cohabitation with a male in the absence of mating.
Figure 4: TSA-facilitated partner preference requires OTR- and V1aR-mediated neurotransmission in the female NAcc.
Figure 5: Cohabitation with mating induces an upregulation of OTR and V1aR in the NAcc of female prairie voles.

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We also thank M. Manning for the generous gift of the OTR antagonist OTA(T) (University of Toledo). This work was supported by grants from the National Institute of Mental Health (MHR21-083128 to M.K. and Z.W., and MHR01-058616 to Z.W.).

Author information

H.W., F.D. and Y.L. performed the experiments. H.W. and F.D. analyzed the data. H.W., F.D., Z.W. and M.K. designed the study. F.D., Z.W. and M.K. wrote the paper. All of the authors discussed the results and commented on the manuscript.

Correspondence to Zuoxin Wang or Mohamed Kabbaj.

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Wang, H., Duclot, F., Liu, Y. et al. Histone deacetylase inhibitors facilitate partner preference formation in female prairie voles. Nat Neurosci 16, 919–924 (2013). https://doi.org/10.1038/nn.3420

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