What Do We Really Know About 5-HT_1A Receptor Signaling in Neuronal Cells?

Serotonin (5-HT) is a neurotransmitter that plays an important role in neuronal plasticity. Variations in the levels of 5-HT at the synaptic cleft, expression or dysfunction of 5-HT receptors may alter brain development and predispose to various mental diseases. Here, we review the transduction pathways described in various cell types transfected with recombinant 5-HT_1A receptor (5-HT_1AR), specially contrasting with those findings obtained in neuronal cells. The 5-HT_1AR is detected in early stages of neural development and is located in the soma, dendrites and spines of hippocampal neurons. The 5-HT_1AR differs from other 5-HT receptors because it is coupled to different pathways, depending on the targeted cell. The signaling pathway associated with this receptor is determined by G_α isoforms and some cascades involve βγ signaling. The activity of 5-HT_1AR usually promotes a reduction in neuronal excitability and firing, provokes a variation in cAMP and Ca²⁺, levels which may be linked to specific types of behavior and cognition. Furthermore, evidence indicates that 5-HT_1AR induces neuritogesis and synapse formation, probably by modulation of the neuronal cytoskeleton through MAPK and phosphoinositide-3-kinase (PI3K)-Akt signaling pathways. Advances in understanding the actions of 5-HT_1AR and its association with different signaling pathways in the central nervous system will reveal their pivotal role in health and disease.