Ketamine upregulates eNOS expression in human astroglial A172 cells: Possible role in its antidepressive properties

•Ketamine increased eNOS gene expression in human astroglial cells.•The effect was mediated by NMDA receptor and Akt inhibition and activation of ERK.•The effect was synergistically augmented by rapamycin.

Ketamine is a potent anti-depressive agent. Nitric oxide plays an essential role in neuronal transmission and cerebral blood flow and has been implicated in the pathophysiology of major depressive disorder as well as cardiovascular functioning. We investigated the effect of ketamine on eNOS expression in human A172 astroglial cells. Ketamine (50-500 μM) increased eNOS expression at 4-24 h in a concentration-dependent manner. This effect was mediated by NMDA receptor, Akt inhibition and ERK1/2 activation and was synergistically augmented by rapamycin. The combined effect on the vascular, immune and neuronal systems may be relevant to the rapid antidepressive effect of ketamine.

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