Effects of fluoxetine on changes of GLT-1 in rat prefrontal cortex after chronic unpredictable stress / 中国药理学通报

ABSTRACT

Aim To investigate the effects of fluoxe-tine on the changes of of protein levels of GLT-1 in pre-frontal cortex in rat depression model, and to further explore the molecular mechanism of antidepressant ac-tion of fluoxetine. Methods Sixty male SD rats were randomly assigned into three groups control group, chronic unpredictable stress ( CUS) group, and CUS+fluoxetine group. The rats of CUS group and CUS+flu-oxetine group were subjected to CUS for 2 sessions per day for 35 days. Then, the rats of the CUS+fluoxetine group were given fluoxetine for 28 days. Behavioral changes were assessed by the sucrose preference and open field tests. The GLT-1 protein levels in the pre-frontal cortex were detected by immunohistochemistry and Western blot analysis at the end of the fluoxetine treatment. Results ( 1 ) Compared with the control group,sucrose preference, total traveling distance, ve-locity and frequencies of rearing were reduced in the CUS group ( P < 0. 01 ) . These behavioral changes could be reversed after 28 day fluoxetine treatment. (2 ) Immunohistochemistry assay indicated weak im-munoreactivity for GLT-1 in the prefrontal cortex of CUS group ( versus the control rats P <0. 01 ); the immunoreactivity for GLT-1 of the fluoxetine-treated rats was significantly up-regulated compared with the CUS group rats ( P<0. 01 ) . ( 3 ) Western blot analy-sis indicated significant reductions of GLT-1 in the pre-frontal cortex of CUS group ( versus the control ratsP<0. 01 ) , and chronic fluoxetine treatment reversed the CUS-induced decrease in GLT-1 levels ( P <0. 01 ) . Conclusions Chronic unpredictable stress ( CUS ) could down-regulate the GLT-1 protein levels in the prefrontal cortex, which is reversed by fluoxe-tine. These results further support the notion that en-hanced expression of the GLT-1 protein could be mo-lecular mechanism of fluoxetine antidepressant effect.