Serotonergic Modulation of Glutamate Neurotransmission as a Strategy for Treating Depression and Cognitive Dysfunction
Document Type
Article
Publication Date
1-1-2014
Journal / Book Title
CNS Spectrums
Abstract
Monoamine-based treatments for depression have evolved greatly over the past several years, but shortcomings such as suboptimal efficacy, treatment lag, and residual cognitive dysfunction are still significant. Preclinical and clinical studies using compounds directly targeting glutamatergic neurotransmission present new opportunities for antidepressant treatment, with ketamine having a surprisingly rapid and sustained antidepressant effect that is presumably mediated through glutamate-dependent mechanisms. While direct modulation of glutamate transmission for antidepressant and cognition-enhancing actions may be hampered by nonspecific effects, indirect modulation through the serotonin (5-HT) system may be a viable alternative approach. Based on localization and function, 5-HT can modulate glutamate neurotransmission at least through the 5-HT1A, 5-HT1B, 5-HT3, and 5-HT7 receptors, which presents a rational pharmacological opportunity for modulating glutamatergic transmission without the direct use of glutamatergic compounds. Combining one or more of these glutamate-modulating 5-HT targets with 5-HT transporter inhibition may offer new therapeutic opportunities. The multimodal compounds vortioxetine and vilazodone are examples of this approach with diverse mechanisms, and their different clinical effects will provide valuable insights into serotonergic modulation of glutamate transmission for the potential treatment of depression and associated cognitive dysfunction.
DOI
10.1017/S1092852913000540
MSU Digital Commons Citation
Pehrson, Alan and Sanchez, Connie, "Serotonergic Modulation of Glutamate Neurotransmission as a Strategy for Treating Depression and Cognitive Dysfunction" (2014). Department of Psychology Faculty Scholarship and Creative Works. 441.
https://digitalcommons.montclair.edu/psychology-facpubs/441
Published Citation
Pehrson, A. L., & Sanchez, C. (2014). Serotonergic modulation of glutamate neurotransmission as a strategy for treating depression and cognitive dysfunction. CNS Spectrums, 19(2), 121–133. doi:10.1017/S1092852913000540
Comments
The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence . The written permission of Cambridge University Press must be obtained for commercial re-use.