Effects of chronic social defeat stress on MAP kinase cascade.

Chronic psychological and social stress can cause psychiatric disorders in humans. In this study, we analyzed the mitogen-activated protein kinase (MAPK) cascade in the hippocampus of chronically socially defeated rats. The rats that were subjected to social defeat every day for 5 weeks showed physiological and behavioral changes, including a reduced rate of weight gain, enlarged adrenal glands, and increased immobility in the forced swim test without concomitant changes in locomotor activity in the open field test. Altered body weight and enlarged adrenal glands are typical symptoms of human depression. Prolonged immobility in the forced swim test indicates behavioral despair, a well-established index of depression. Because the MAPK cascade plays a pivotal role in depression, we quantified the expression of these molecules in the hippocampus of chronically defeated rats using western blot analysis. We found that phospho-MAPK kinases 1/2 (MEK1/2) and phospho-extracellular signal-regulated kinases 1/2 (ERK1/2) were decreased, whereas MAPK phosphatase-1 (MKP-1) was increased in the hippocampus of chronically defeated rats compared to the control group. These results were consistent with findings in depressed patients and other animal models of depression. In conclusion, our findings suggest that chronic psychosocial stress in Wistar rats induced depression-like behavior and downregulated the MAPK cascade in the hippocampus.