Serotonin and neuronal growth factors - a convergence of signaling pathways

Monoamines, including serotonin (5-HT), have traditionally been associated with short-term signaling pathways in neurons, such as the modulation of cAMP and Ca2+ levels. In contrast, neuronal growth factors, such as neurotrophins, have been traditionally associated with signaling pathways, such as those for activation of extracellular-regulated kinase (ERK) and Akt (protein kinase B), which are known to induce long-term protective changes. It has therefore been unclear how antidepressants that increase serotonin (5-HT), induce such changes as hippocampal neuroprotection and neurogenesis. It has been hypothesized, that the actions of 5-HT may be mediated indirectly through increased synthesis of peptide growth factors. However, there is increasing evidence that some subtypes of 5-HT receptors can directly couple to activation of the ERK and Akt pathways. Such coupling suggests a more direct potential role for 5-HT in mediating the long-term actions induced by antidepressants.