D ISTRIBUTION OF SEROTONIN RECEPTOR OF TYPE 6 IN HUMAN BRAIN POST -

Abstract

D ISTRIBUTION OF SEROTONIN RECEPTOR OF TYPE 6 IN HUMAN BRAIN POST -

MORTEM . A pharmacology, autoradiography and immunohistochemistry study.

The neurotransmitter 5-hydroxytryptamine (5-HT), known as serotonin, is acknowledged, since long time ago, to be able to influence anxiety and depression, as well as various physiological functions such as sleep feeding behavior, sexuality, mood and circadian rhythms.

Hence, the most part of the research about the 5-HT are focused on these fields. However, more attention has been recently directed to the relationship between 5-HT neurotransmission and memory.

The serotonin receptors of type 6 (5-HT6R) are recently identified. They are quiet different from all the other 5-HT receptors, because they are characterized by a short third cytoplasmatic loop and a long C-terminal tail, and because they contain one intron, located in the middle of the third cytoplasmatic loop. After some initial controversies, the available findings are now apparently more congruent. Nevertheless, the discrepancies concerning, for example, the binding affinity, the effects of 5-HT6 ligands on brain catecholamines and the behavioral syndromes mediated by them, still exist. Much interest on 5-HT6 receptors was triggered by the evidence that some antipsychotics could bind to them. Subsequently, despite the lack of completed informations on metabolic patterns of the various compounds, some of 5-HT6 receptor ligands entered the clinical development as potential anti-dementia, antipsychotic and anti-obese drugs. Anyway, the available information on both the pharmacology of 5-HT6 receptors is still quite inadequate.

The purpose of this study was to investigate the distribution of 5-HT6 receptors in some

human brain areas obtained postmortem, by means of binding techniques, and to characterize

them pharmacologically where possible. In addition, autoradiography of brain sections were

performed, as well as immunohistochemistry and immunofluorescence for a better

localization of the receptors.