Astrocytes activation contributes to the antidepressant-like effect of ketamine but not scopolamine

Depression is a common, debilitating mood disorder, but currently available antidepressants have several major drawbacks. Both ketamine and scopolamine attract more and more attention due to their rapid and sustained antidepressant activities. However, the molecular and cellular mechanism that underlies the therapeutic action of ketamine and scopolamine still remain to be elucidated. Considering the importance of astrocytes in the development of depression, we hypothesized that the activation of astrocyte may play a vital role in the antidepressant effects of ketamine and scopolamine. In the present study, the expression of fibrillary acidic protein (GFAP) was detected to evaluate the activation of astrocyte after single injection of ketamine and scopolamine in respective efficient doses. Behavioral tests used to assess antidepressant-like effects were forced swim test (FST) and tail suspension test (TST). Fluorocitrate, a well-established astrocyte inactivator, was adopted to inhibit the activation of astrocyte. The results demonstrated that ketamine, but not scopolamine, could increase significantly the expression of GFAP in hippocampus. In addition, inhibition of astrocyte abolished the antidepressant-like effects of ketamine, but not scopolamine in the FST and TST. It is suggested that activated astrocyte plays a vital role in the antidepressant activities of ketamine rather than scopolamine. These findings may be important for the understanding of the role of astrocyte in depression and antidepressants, especially rapid antidepressants.