Involvement of hippocampal serotonin and neuropeptide Y in depression induced by chronic unpredicted mild stress

Accumulated evidence indicates a role of the hippocampal 5-hydroxy-tryptamine (5-HT) and neuropeptide Y (NPY) in the response to stress and modulation of depression, but it is unclear whether and how the hippocampal 5-HT and NPY systems make contributions to chronic unpredicted mild stress (CUMS)-induced depression. Here we observed that rats receiving a variety of chronic unpredictable mild stressors for 3 weeks showed a variety of depression-like behavioral changes, including a significant reduction in body weight, sucrose preference, and locomotion, rearing and grooming in open field test, and a significant increase in immobility time in forced swimming test. These CUMS-induced behavioral changes were suppressed or blocked by intra-hippocampal injection of 5-HT (31.25 μg/μl) or NPY (10 μg/μl). These data suggest a critical role of reduced hippocampal 5-HT and NPY neurotransmission in CUMS-induced depression.