Handbook of the Behavioural Neurobiology of Serotonin.

Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine, which works as an autacoid in the periphery and as a neurotransmitter in the central nervous system (CNS). It is synthetized from the essential amino acid tryptophan. In the CNS, the first rate-limiting step of tryptophan conversion to 5-hydroxytryptophan is accomplished by tryptophan hydroxylase 2 (TPH2). This enzyme is expressed exclusively in serotonergic neurons and does not contribute to the serotonin synthesis in the periphery. Mice and rats with genetic deletion of Tph2 were generated by several laboratories. These animals lack central 5-HT, and therefore, represent unique models for elucidating the functions of brain 5-HT in development, physiology, and behavior. TPH2-deficient animals are viable and exhibit only slight alterations in serotonergic wiring in the brain. Nevertheless, central 5-HT depletion affects several phenotypes which are consistently observed in different species and laboratories, such as postnatal growth retardation, maternal neglect, decreased anxiety, and exacerbated aggression. Surprisingly, rodents lacking central serotonin do not’ show clear-cut changes in depression-like behavior, in contrast to previous pharmacological studies targeting the serotonergic system. The exaggerated aggression and reduced anxiety in TPH2-deficient animals render them a valuable model for several psychiatric diseases, such as autism and attention-deficit hyperactivity disorder. In this chapter we will focus on functions of TPH2 and describe the behavioral outcomes of its genetic deletion in rodents.