Effect of chronic mild stress and imipramine on the proteome of the rat dentate gyrus

J. Neurochem. (2010) 113 , 848–859. Abstract The present study uses a proteomic approach to examine possible alterations of protein expression in the hippocampus of rats that are subjected to chronic mild stress (CMS). These rats serve as an animal model that was developed to mimic anhedonia, which is one of the core symptoms of depression. As antidepressant treatment is effective after a few weeks of administration, we also aimed to identify changes that were linked to chronic (once daily for 4 weeks) and ‘pulse’ (once a week) administration of imipramine. Fifteen differential proteins were identified with 2D electrophoresis followed by mass spectrometry. Although both methods of imipramine administration restored normal sucrose consumption in rats that were subjected to CMS, the molecular mechanisms of these two therapies were different. CMS‐induced changes in the levels of dynactin 2, Ash 2, non‐neuronal SNAP25 and alpha‐enolase were reversed by chronic imipramine, but ‘pulse’ treatment was not that effective.