Objective:To research the effect of restraint stress and glucocorticoid on the expression of AMPA receptors Glu R2 subunit

NMDA receptor NR2 B subunit and the intervention effect of CP-154526. Methods:A total of 30 male Sprague-Dawley rats were randomly divided into 3 groups :restraint stress group(10 rats receiving restraint stress once a day over a period of 21 days);CP-154526 treatment group(10 rats receiving restraint stress and intraperitoneal injection of CP-154526 once a day over a period of 21days);control group(10 rats receiving no restraint stress and no intervention of CP-154526). Sprague-Dawley rats received restraint stress for 3 h daily over a period of 21 days to make the depression model. Then the behaviors of rats were observed by tail suspension test and forced swimming test. The levels of glucocorticoid in rat blood serum were observed by enzyme-linked immunosorbent assay. And the expression of AMPA receptors Glu R2 subunit and NMDA receptor NR2 B subunit in hypothalamus were observed through immunohistochemical assay and the correlation between results was assessed. Results:In the tail suspension test

the immobility times in control group

stress group

CP-154526 treatment group were(118.40±27.36)s

(191.00±28.84)s

(141.60±23.89)s;stress group showed increased immobility time compared with that of control group(P=0.001)and CP-154526 treatment group(P=0.013). In the forced swimming test

the swimming immobility times in control group

stress group

CP-154526 treatment group were(87.20±14.49)s

(145.80±17.45)s

(106.60±14.01)s and the swimming immobility time of stress group was higher than that of control group(P=0.000)and CP-154526 treatment group(P=0.002).The serum GC concentration in the control group

stress group

CP-154526 treatment group were(52.61 ±6.11)μg/L

(194.33 ±23.30)μg/L

(64.17±19.59)μg/L

and the stress group showed significant increase in the serum glucocorticoid concentration compared with that of control group(P=0.000)and CP-154526 treatment group(P=0.000). In the immunohistochemistry experiments

the average optical density value of Glu R2 subunit in control group

stress group

CP-154526 treatment group were 0.227±0.031

0.079±0.011

0.169±0.020

the average optical density value of Glu R2 subunit in the stress group was lower than that of control group(P=0.000)and CP-154526 treatment group(P=0.000). The average optical density value of Glu R2 subunit in the CP-154526 treatment group was lower than that of control group(P=0.000). The average optical density value of NR2 B subunit in the control group

stress group

CP-154526 treatment group were 0.159 ±0.021

0.266 ±0.054

0.168 ±0.018

and the average optical density value of NR2 B subunit in the stress group was higher than that of control group(P =0.000)and CP-154526 treatment group(P =0.000). The tail suspension immobility times and swimming immobility times were positively correlated with serum GC level and the expression of NR2 B subunit(r=0.721

P=0.006;r=0.589

P=0.153;r=0.486

P=0.004;r=0.868

P=0.000). But tail suspension immobility times and swimming immobility times were negatively correlated with the expression of Glu R2 subunit(r=-0.721

P=0.014;r=-0.812

P=0.012). Conclusion:Plasma concentration of glucocorticoid after chronic stress is increased

and the glutamate receptor in the hypothalamus is changed. The up-regulation of expression of NR2 B subunit and down-regulation of expression of Glu R2 subunit in hypothalamus are related with the behavioral despair. The CP-154526 can improve the behavioral despair of rats with chronic stress.