Objective      To determine the effect of chronic restraint stress on the expression of brain derived neurotrophic factor (BDNF) and growth associated protein 43 (GAP-43) in the hypothalamus of rats

the role of BDNF and GAP-43 in the pathogenesis of depression induced by chronic restraint stress

and the regulation effect of CP-154526 [corticotrophin-releasing hormone type 1 receptor (CRH1R) antagonist].       Methods      A total of 30 male Sprague-Dawley rats were randomly divided into 3 groups: restraint stress group

CP-154526 treatment group and control group. The rats were restrained for 3 h daily over a period of 21 d to construct depression model. The treatment group was injected with CP-154526 from the beginning of the experiment

while the control group was injected with dimethyl sulfoxide (solvent of CP-154526). Then the behaviors of the rats were observed. The level of corticotrophin-releasing hormone (CRH) in the blood serum was detected by enzyme-linked immunosorbent assay(ELISA)

and the expression of BDNF and GAP-43 in the hypothalamus was verified by Western blotting.       Results      Compared with the control group and the CP-154526 treatment group

the restraint stress group showed decreased body weight (P0.05)

reduced sucrose preference (P0.05)

and decreased spanning lattice times

standing times and modification times (P0.05). There was no statistical difference between the CP-154526 treatment group and the control group in the above tests (P0.05). The restraint stress group showed significant increase in the serum CRH concentration compared with the control group (P0.05)

but there was no significant difference between the CP-154526 treatment group and the control group (P0.05). Compared with the control group and CP-154526 treatment group

the restraint stress group showed higher expression of BDNF and GAP-43 in the hypothalamus (P0.05).       Conclusion      Chronic restraint stress can induce up-regulation of BDNF protein and GAP-43 protein in the hypothalamus

and lead to plastic changes in the hypothalamus

which are consistent with the changes of CRH secretion and depression-related behavior. CP-154526 significantly alleviates the symptoms of depression through inhibiting the up-regulation of BDNF protein and GAP-43 protein in the hypothalamus.