Time-dependent modulation of glutamate synapses onto 5-HT neurons by antidepressant treatment

Neuropharmacology
Sean D GeddesJean-Claude Béïque

Abstract

Antidepressants, including the selective serotonin reuptake inhibitors (SSRIs), are thought to exert their clinical effects by enhancing serotonin (5-HT) transmission. However, animal studies show that the full magnitude of this enhancement is reached only following prolonged treatments with SSRIs, consistent with the well-described therapeutic delay of this class of medications. Thus, the clinical efficacy of SSRIs most likely does not emerge from their acute pharmacological actions, but rather indirectly from cellular alterations that develop over the course of a sustained treatment. Here, we show that sustained administration of the SSRI citalopram leads to a homeostatic-like increase in the strength of excitatory glutamate synapses onto 5-HT neurons of the dorsal raphe nucleus that was apparent following one week of treatment. A shorter treatment with citalopram rather induced a paradoxical decrease in the strength of these synapses, which manifested itself by both pre- and postsynaptic mechanisms. As such, these results show that an SSRI treatment induced a concerted and time-dependent modulation of the synaptic drive of 5-HT neurons, which are known to be critically involved in mood regulation. This regulation, and its ti...Continue Reading

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Citations

Mar 5, 2016·Pharmacological Reports : PR·Kamil BieniasHalina Car
Apr 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Sean D GeddesJean-Claude Béïque
Feb 6, 2019·Advances in Pharmacological Sciences·Mervin Chávez-CastilloJoselyn Rojas-Quintero
Feb 27, 2019·ACS Chemical Neuroscience·Kathryn G Commons, Sofia E Linnros

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