Selective serotonin reuptake inhibitors (SSRIs) have different acute and long-term effects, but the reasons are unclear. Researchers may have solved this mystery by showing that serotonergic neurons release both serotonin and glutamate, thereby transmitting a dual signal with behaviourally distinct effects.
Writing in Trends in Cognitive Sciences (online, 17 December 2014)
, the team notes that the serotonergic component is immediately amplified following SSRI administration, whereas the glutamate component is suppressed in the acute phase and normalises only after several days of SSRI therapy.
The initial reduction in glutamate could explain why SSRIs have a delayed onset of therapeutic effect in depression, say the authors. It could also lead to new drug targets aimed at bridging the delayed action and increasing therapeutic efficacy.