In this study, we made the following discoveries: (i) CUMS-exposed rats treated with SSD exhibited increased body weight and food intake, with a reduction in depression-like behaviors; (ii) SSD administration decreased glutamate levels in the rats’ CA1 region of CUMS-exposed; (iii) SSD treatment resulted in downregulated Homer1b/c expression as well as upregulated mGluR5, mTOR, PSD-95, and SYP expression, and increased p-mTOR/mTOR, p-p70S6k/p70S6k, and p-4E-BP1/4E-BP1 expression ratios in the CUMS-exposed rats’ CA1 region. Here, RPS6KB1 is linked to major depressive disorder.