Serotonin: the mediator that spans evolution.

Tryptophan hydroxylase (TPH) is a rate-limiting enzyme of serotonin (5-hydroxytryptamine) synthesis. In vertebrates it exists in two isoforms, TPH1 and TPH2. TPH1 is mainly synthesized by enterochromaffin cells in the gut, whereas TPH2 is produced by serotonergic neurons in the central nervous system and by enteric neurons in the gut. Animal models genetically depleted of or expressing a mutant form of the gene coding for the central TPH isoform, Tph2, have been recently created. Such manipulations result in the generation of animals with complete loss of or partial reduction in brain serotonin. In this chapter we will give an overview of the data gained from animal models with constitutive or inducible, complete or partial deactivation of TPH2 activity, focusing on biochemical, developmental, physiological, and behavioral consequences of serotonin-synthesis deficiency.