5-HT1A receptor-regulated signal transduction pathways in brain

Abstract

Serotonin is an influential monoamine neurotransmitter that signals through a number of receptors to modulate brain function. Among different serotonin receptors, the serotonin 1A (5-HT1A) receptors have been tied to a variety of physiological and pathological processes, notably in anxiety, mood, and cognition. 5-HT1A receptors couple not only to the classical inhibitory G protein-regulated signaling pathway, but also to signaling pathways traditionally regulated by growth factors. Despite the importance of 5-HT1A receptors in brain function, little is known about how these signaling mechanisms link 5-HT1A receptors to regulation of brain physiology and behavior. Following a brief summary of the known physiological and behavioral effects of 5-HT1A receptors, this article will review the signaling pathways regulated by 5-HT1A receptors, and discuss the potential implication of these signaling pathways in 5-HT1A receptor-regulated physiological processes and behaviors.

Figure 1

5-HT1A Receptor-regulated Signal Transduction Pathways. 5-HT, serotonin; 5-HT1A, serotonin 1A receptors; Gi, inhibitory Guanine nucleotide binding protein; AC, adenylyl cyclase; cAMP, cyclic adenosine monophosphate; GIRK, G-protein coupled inward rectifying potassium channel; GFR, growth factor receptor; PKA, protein kinase A; CREB, cAMP response element binding protein; MEK1/2, MAP and ERK kinase 1/2; ERK 1/2, extracellular signal-regulated kinase 1/2; RSK, ribosomal S6 kinase; PI3K, phosphotidylinositol-3 kinase; PDK, phosphoinositide dependent kinase; GSK3, glycogen synthase kinase-3; FoxO, forkhead box O transcription factors