Role of TPH-2 in brain function: news from behavioral and pharmacologic studies

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.