Abstract
The recent discovery of TPH‐2, a new isoform of tryptophan hydroxylase, the enzyme that catalyses the transformation of tryptophan into 5‐hydroxytryptophan and the rate‐limiting step in brain serotonin (5‐HT) biosynthesis, has boosted new interest in the many functions of 5‐HT in the brain and non‐nervous tissues. Recent studies on TPH‐2 are reviewed with particular attention to the role of this enzyme in behavior and in response to drugs as assessed by comparing strains of mice carrying a functional polymorphism of TPH‐2. Most studies concur to indicate that 5‐HT synthesis through TPH‐2 influence nervous tissues whereas TPH‐1 is responsible for the synthesis and action of 5‐HT in peripheral organs. Partial impairment of brain 5‐HT synthesis caused by polymorphism of the gene encoding TPH‐2 causes reduced release of the neurotransmitter, increased aggressiveness, and alters the response to drugs inhibiting the reuptake of 5‐HT. Strain comparison might be a useful strategy to investigate the genotype‐dependent alterations of TPH‐2. © 2007 Wiley‐Liss, Inc.