The possible role of 5-HT(1B/D) receptors in psychiatric disorders and their potential as a target for therapy

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is implicated in several psychiatric diseases. Is this also true for 5-HT(1B/D) receptors? These receptors are found in high density in substantia nigra, globus pallidus, striatum and basal ganglia and in other brain regions. This ubiquity makes 5-HT(1B/D) receptors responsible for many physiological and behavioural functions. This review focuses on the role of 5-HT(1B) receptors in the regulation of 5-HT release and synthesis. Microdialysis experiments performed on freely moving animals are an interesting in vivo model to study the function of the terminal 5-HT(1B) autoreceptor. Synthesis of 5-HT, estimated by the measurement of the accumulation of 5-hydroxytryptophan (5-HTP) ex vivo or in vitro, is modulated by the 5-HT(1B) autoreceptors. Many reports have shown that chronic administration with selective serotonin reuptake inhibitors leads to the desensitisation of the terminal 5-HT(1B) autoreceptors. With the help of some animal models of depression and anxiety and with some data from clinical studies it has been hypothesised that 5-HT(1B) receptors may be supersensitive in depression, anxiety and obsessive compulsive disorder. Thus, since the dysfunction of 5-HT(1B) receptors may be involved in some pathological states, particularly in the psychiatric field, these receptors represent important potential targets for drugs to treat mental diseases.