Selective serotonin reuptake inhibitors (SSRIs) are key drugs for the treatment of depression and anxiety disorders. Although the SSRIs rapidly block 5-hydroxytryptamine uptake, the clinical effects of the drug require several weeks of treatment. Long-term antidepressant exposure does lead to synaptic rearrangements that are cAMP signaling-mediated. In this issue, Zhang and Rasenick evaluated Gαs protein coupling to adenylate cyclase in the glioma C6 cell line that lacks serotonin reuptake transporters (SERTs). The C6 cells were treated with the efficacious SSRI escitalopram or S-citalopram and its inactive enantiomer R-citalopram. Over time, only escitalopram increased adenylate cyclase activity via increased translocation of Gαs protein from lipid raft domains leading to more effective activation of the cyclase. These observations suggest that the antidepressant activity of the SSRIs could involve pre- and postsynaptic targets other than the SERTs.
See article at J Pharmacol Exp Ther 2010, 332:977–984.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics