Ghrelin produces antidepressant-like effect in the estrogen deficient mice.

Recent evidence shows that ghrelin plays an important role in depression. However, it was little known whether ghrelin produces antidepressant-like effect in the ovariectomized mice. The present study was aimed to investigate the antidepressant-like effects of the ghrelin in ovariectomized mice. In the forced swim test, ghrelin significantly decreased immobility time, reversing the "depressive-like" effect observed in ovariectomized mice, and this effect was reversed by the tamoxifen. In addition, immunohistochemical study indicated that ghrelin treatment reversed the reductions in c-Fos expression induced by ovariectomy. An estrogen antagonist tamoxifen also antagonized the effect of ghrelin on the c-Fos expression. Furthermore, the western blotting indicated that brain-derived neurotrophic factor (BDNF) in the hippocampus, but not phosphorylated cAMP response element-binding protein (pCREB)/CREB in the frontal cortex, were affected by ghrelin treatment. Ghrelin treatment significantly increased BrdU expression. Therefore, these findings suggest that ghrelin produces antidepressant-like effects in ovariectomized mice, and estrogen receptor may be involved in the antidepressant-like effects of the ghrelin.