Abstract

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 (5â�?�?�?�?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 5â�?�?�?�?HT, provided that such strategies would directly target 5â�?�?�?�?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 5â�?�?�?�?HT4 agonists and 5â�?�?�?�?HT7 antagonists.