Extensive preclinical research has focused at unravelling the underlying molecular mechanisms leading to depression and recovery. In this study, we investigated the quantitative changes in protein abundance in the ventral hippocampal granular cell layer. We compared different phenotypes from the chronic mild stress (CMS) model of depression using chronic administration with two selective serotonin reuptake inhibitors (SSRIs), escitalopram and sertraline. We isolated granular cells using Laser-Capture Microdissection (LCM) and we identified their regulated proteins using two-dimensional (2D) differential gel electrophoresis (DIGE) and tandem mass spectrometry (MS/MS). The majority of the proteins we identified were enzymes involved in different metabolic activities. Additional proteins were functionally classified as vesicular proteins and immune system proteins. Rab GDP dissociation inhibitor alpha (GDIA) and syntaxin-binding protein 1 (STXB1) were potential markers for stress reactivity. Dynamin 1 (DYN1), glutathione S-transferase omega-1 (GSTO1) and peroxiredoxin (PRDX6) were associated with treatment response. In addition, an imbalance between different post-translationally modified versions of DYN1 and GSTO1 potentially accounted for SSRI treatment refraction. In the present study, we searched for new markers of stress reactivity and treatment response as well as any underlying molecular mechanisms correlating to the development of anhedonia and antidepressant therapy refraction. Our results pointed towards an essential role of post-translational modifications in both vesicular and immune protein systems.