Distribution of 5-HT receptors in the central nervous system

Abstract

Thealmost incredible complexity of the 5-HT receptor family translates into the diversity of the brain distribution of these receptors, as briefly illustrated in this chapter. However, the picture is by no means complete, due either to the lack of tools for some of these receptors or their components (selective ligands or good antibodies that label exclusively a single receptor are still rare) and/or to the genomic complexity of some of these receptors; thus 5-HT 4 and 5-HT 7 receptors come in numerous splice variants, the 5-HT 2C receptor has even more potential editing variants, whereas the 5-HT 3 receptor has multiple potential subunits. There is debate as to which of the latter are co-expressed and form functional receptors, or which splice/editing variants of the former are expressed and where. In addition, one tends to be misled by density – for example, the 5-HT 2C receptor is not only a choroid plexus receptor, the dorsal raphe nucleus expresses more than just 5-HT 1A receptors, and it may be premature to suggest that the low density of 5-HT 3 receptors outside of the brainstem has low functional relevance. The 5-HT 1e receptor is not expressed in rodents, and 5-HT 5b receptors do not exist in man; in addition, both receptors share an almost total lack of adequate tools for their identification. On the other hand, we have tried to illustrate the fact that initial receptor distribution studies have been crucial in the definition of new 5-HT receptors, especially in the days preceding molecular biology/receptor cloning, and that the knowledge of receptor distribution in health and disease is essential for a (patho)physiological understanding of their function