Role of 5-HT(3) Receptors in the Antidepressant Response

Serotonin (5-HT)(3) receptors are the only ligand-gated ion channel of the 5-HT receptors family. They are present both in the peripheral and central nervous system and are localized in several areas involved in mood regulation (e.g., hippocampus or prefrontal cortex). Moreover, they are involved in regulation of neurotransmitter systems implicated in the pathophysiology of major depression (e.g., dopamine or GABA). Clinical and preclinical studies have suggested that 5-HT(3) receptors may be a relevant target in the treatment of affective disorders. 5-HT(3) receptor agonists seem to counteract the effects of antidepressants in non-clinical models, whereas 5-HT(3) receptor antagonists, such as ondansetron, present antidepressant-like activities. In addition, several antidepressants, such as mirtazapine, also target 5-HT(3) receptors. In this review, we will report major advances in the research of 5-HT(3) receptor's roles in neuropsychiatric disorders, with special emphasis on mood and anxiety disorders.