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Connection re-established: neurotransmission between the medial prefrontal cortex and serotonergic neurons offers perspectives for fast antidepressant action

Author(s): Adeline Etievant, Laura Lambas-Senas, Erika Abrial, Cecile Betry, Nasser Haddjeri, Guillaume Lucas

The search for fast-acting antidepressants has been a major challenge in neuropsychopharmacology for many years. Although the involvement of serotonin (5‑HT) in the mechanisms of action of classical antidepressants has been clearly established, the delayed onset of action of these drugs prompted several authors to propose alternative targets in order to achieve a more rapid relief of symptoms in depressed patients. However, recent studies indicate that it may be possible to elaborate fast-acting antidepressant strategies based on 5‑HT, provided that such strategies would directly target 5‑HT neuron electrical activity. Furthermore, glutamatergic pyramidal neurons projecting from the medial prefrontal cortex to the dorsal raphé appear to play a critical role. This article presents some of the data that support this hypothesis, including results from medial prefrontal cortex deep-brain stimulation studies, as well as those related to treatments with 5‑HT4 agonists and 5‑HT7 antagonists.


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