Abstract: Neuropeptide Y (NPY), a conservative neuroendocrine peptides widely expressed in Peripheral and Central nervous system, is associated with depression, anxiety, and digestive disease. To study NPY expression in rat model of depression and to explore the mechanisms of the antidepressants, we developed a rat model of depression by the chronic stress exposure and isolation housing. We randomly divided 36 depressed rats into three groups (n=12) and treated them with fluoxetine-, amitriptyline- and normal saline, respectively. Behavioral changes in these rats were analyzed in an Open-Field paradigm, and compared to a control group of 12 normal rats. The expression patterns of NPY in the hypothalamus were analyzed using Reverse Transcription - Polymerase Chain Reaction (RT-PCR), Western Blot, and the Immunohistochemical assays. We made the following observations:(1) Compared with the normal rats, total traveling distance and activity frequency were reduced (p <0 .01) in the depressed rats; their weight gains were smaller (p <0 .05); and their NPY mRNA levels in the hypothalamus were also lower (p < 0.01); (2) after treatment with either fluoxetine or amytriptyline, NPY mRNA and protein levels increased in brain of depressed rats. This difference is significance when compared to the normal saline group (p< 0.01).; (3) Compared with the normal control group, cell membrane and cytoplasm were stained to brown or yellow in the normal saline-treated group, indicating a positive immunohistochemical reaction. In contrast, the cell membrane and cytoplasm were stained to a color similar to the background color in the fluoxetine- and amytriptyline-treated groups, indicating a weak or negative immunohistochemical reaction. These results suggest that the brain NPY expression is reduced in the brain of depressed rats, and that a possible mechanism of the antidepressants is via enhancing rat brain NPY expression.

Key words: Depression, Amitriptyline, Chronic stress, Fluoxetine, Neuropeptide Y