Trichostatin A (TSA) facilitates formation of partner preference in male prairie voles (Microtus ochrogaster)

Abstract

In the socially monogamous prairie voles (Microtus ochrogaster), the development of a social bonding is indicated by the formation of partner preference, which involves a variety of environmental and neurochemical factors and brain structures. In a most recent study in female prairie voles, we found that treatment with the histone deacetylase inhibitor trichostatin A (TSA) facilitates the formation of partner preference through up-regulation of oxytocin receptor (OTR) and vasopressin V1a receptor (V1aR) genes expression in the nucleus accumbens (NAcc). In the present study, we tested the hypothesis that TSA treatment also facilitates partner preference formation and alters OTR and V1aR genes expression in the NAcc in male prairie voles. We thus observed that central injection of TSA dose-dependently promoted the formation of partner preference in the absence of mating in male prairie voles. Interestingly, TSA treatment up-regulated OTR, but not V1aR, gene expression in the NAcc similarly as they were affected by mating - an essential process for naturally occurring partner preference. These data, together with others, not only indicate the involvement of epigenetic events but also the potential role of NAcc oxytocin in the regulation of partner preference in both male and female prairie voles.

Keywords: Nucleus accumbens; Oxytocin; Partner preference; Prairie voles; Trichostatin A; Vasopressin.

Figure 1

Trichostatin A (TSA) facilitates partner preference formation in male prairie voles in the absence of mating. (A) Males injected with artificial cerebrospinal fluid (CSF) spent a similar amount of time in side-by-side contact with the partner and stranger female, while males receiving an acute injection of 0.08 ng TSA, but not higher doses, spent preferentially more time with the partner than with the stranger during the partner preference test. Similarly, only males treated with 0.08 ng TSA exhibited a partner preference index (B) positive and higher than CSF-treated voles. Neither locomotor activity (C), nor total time spent interacting with either stimulus female (D) was affected by TSA treatment at any dose. In (A,C,D), the number of animals per group is represented within each column, and data are presented as mean ± SEM. *p < 0.05 vs “Stranger” of the same biological group, paired two-tailed t test. In (B), data are represented as whisker-plot where the horizontal bar corresponds to the median, and each animal is depicted as individual black dot. ^#p < 0.05 vs. an index of “0”, Wilcoxon signed ranked test.

Figure 2

Trichostatin A (TSA, 0.08 ng) up-regulates oxytocin receptor (OTR) but not vasopressin V1a receptor (V1aR) expression in the nucleus accumbens (NAcc) but not caudate putamen (CP) in male prairie voles during cohabitation with a female in the absence of mating. OTR but not V1aR mRNA levels (A) are up-regulated in the NAcc following two hours of cohabitation with a female in the absence of mating in TSA-treated males. Similarly, OTR but not V1aR protein levels are up-regulated in the NAcc (B) of TSA-treated males following 9 hours of cohabitation with a female in the absence of mating. In the CP, however, OTR and V1aR protein levels remained unaffected by TSA treatment (C). In (B,C), representative blots for each target protein (top line) and actin (bottom line) are shown above their respective column. Data are presented as mean ± SEM, and the number of animals per group is detailed within each column. *p < 0.05 vs CSF-treated voles, unpaired two-tailed t test.

Figure 3

Cohabitation with mating for 24 hours with a female induces an up-regulation of oxytocin receptor (OTR) protein levels in the nucleus accumbens (NAcc) but not in the caudate putamen (CP) of male prairie voles. Representative blots for OTR (top line) and actin (bottom line) are shown above their respective column. Data are presented as mean ± SEM, and the number of animals per group is represented within each column. *p < 0.05 vs sexually-naive voles, unpaired two-tailed t test.