What Do We Really Know About 5-HT _1A Receptor Signaling in Neuronal Cells?

摘要

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_(1A)R), specially contrasting with those findings obtained in neuronal cells. The 5-HT_(1A)R is detected in early stages of neural development and is located in the soma, dendrites and spines of hippocampal neurons. The 5-HT_(1A)R 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_(1A)R usually promotes a reduction in neuronal excitability and firing, provokes a variation in cAMP and Ca~(2+), levels which may be linked to specific types of behavior and cognition. Furthermore, evidence indicates that 5-HT_(1A)R 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_(1A)R and its association with different signaling pathways in the central nervous system will reveal their pivotal role in health and disease.