Importantly, LPM570065 was able to significantly ameliorate depression susceptibility in mice experiencing double stress and this effect was at least partially mediated by reversing the methylation of Oxtr. Together, this study extended previous results of the antidepressant-like activity of the triple reuptake inhibitor LPM570065 by revealing a novel epigenetic mechanism of antidepressant actions of this new and potentially important antidepressant drug. This evidence concerns the gene OXTR and depressive disorder.