Antidepressants upregulate messenger RNA levels of the neuroprotective enzyme superoxide dismutase (SOD1)

Objective: To investigate the effect of amitriptyline, bupropion, doxepin o r venlafaxine on the gene expression of the neuroprotective enzyme superoxi de dismutase (SOD I) in a catecholamine cell in vitro model. Design: Molecu lar study of a cultured cell line. Interventions: Rat pheochromocytoma (PC 12) cells were incubated in I and 10 mu mol/L of various antidepressant med ications for 24 or 48 hours. Outcome measures: Northern blot analysis. Resu lts: Amitriptyline up-regulated SODI messenger RNA in a time- and dose-depe ndent manner. The greatest up-regulation was following incubation with 10 m u mol/L amitriptyline for 48 hours. The addition of bupropion, doxepin or v enlafaxine to PC 12 cell cultures also up-regulated SOD I mRNA. Conclusions : These findings suggest that some antidepressants have the ability to posi tively regulate neuroprotective genes.