EP300 and depressive symptom measurement: To verify the role of p300 in depression, we first measured the expression levels of p300 in the mPFC of depressed male and female mice, and found that CUS decreased the mRNA levels of p300 only in male mice (Figure 6A, male: t(18) = 3.0580, p = 0.0068; female: t(14) = 0.1554, p = 0.8787).