5.HT1 receptors in the vertebrate brain

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Abstract
The regional distribution of high affinity [33H]5-HT recognition sites in the brain of several vertebrates (pigeon, rat, mouse, guinea-pig, cat, dog, monkey and human) was analyzed using in vitro autoradiography. The presence of subtypes of 5-HT1 binding sites was investigated by selective displacements with 8-OH-DPAT, mesulergine and (±)SDZ 21-009 at appropriate concentrations to block 5-HT1A, 5-HT1c and 5-HT1B sites respectively. In addition, 5-HT1A, and 5-HT1c sites were directly visualized with the more selective radioligands [3H]8-OH-DPAT and [3H]mesulergine, respectively. In the pigeon brain, total [3H]5-HT binding sites were enriched in all telencephalic areas. Densely labelled regions were also present in the optic tectum and the brainstem. No binding was observed in the cerebellum. 8-OH-DPAT and mesulergine only displaced a small proportion of [3H]5-HT binding in most of the areas where high concentrations of 5-HT1 sites were found. (±)SDZ 21-009 did not affect [3H]5-HT binding in the regions examined. Taking into account our pharmacological studies, these results suggest that the majority of 5-HT1 sites belong to the 5-HT1D subtype in the pigeon brain. In the mammalian species investigated high levels of [3H]5-HT binding were found in the neo-cortex, hippocampal formation, basal ganglia and related structures (substantia nigra), raphe dorsalis, nucleus superior colliculus and choroid plexus. However, these brain areas were differentially enriched in subtypes of 5-HT1 recognition sites. 5-HT1A sites were observed in the neo-cortex, the hippocampal formation and the raphe nucleus, whereas 5-HT1C sites accounted for all 5-HT1 binding in the choroid plexus. In the mouse and rat brain, 5-HT1B binding sites were enriched in the basal ganglia and associated regions (substantia nigra). These areas were enriched in 5-HT1D sites in the brain of the other mammals studied. In these animals, no site with a 5-HT1B pharmacological profile were detected. These results indicate that 5-HT1A 5-HT1c and 5-HT1D sites are present already in the lower vertebrate species investigated and that 5-HT1B appear to be exclusive of the myomorph rodents (mouse, rat). Furthermore, the different subtypes of the 5-HT1, receptors present a conserved regional distribution with the 5-HT1D sites being enriched in the basal ganglia and the 5-HT1A sites predominating in the hippocampal formation.