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Autoradiographic distribution of 5-HT7 receptors in the human brain using [3H]mesulergine: comparison to other mammalian species.

ABSTRACT: 1. The main aim of this investigation was to delineate the distribution of the 5-HT(7) receptor in human brain. Autoradiographic studies in guinea-pig and rat brain were also carried out in order to revisit and compare the anatomical distribution of 5-HT(7) receptors in different mammalian species. 2. Binding studies were performed in rat frontal cortex membranes using 10 nm [(3)H]mesulergine in the presence of raclopride (10 microm) and DOI (0.8 microm). Under these conditions, a binding site with pharmacological characteristics consistent with those of the 5-HT(7) receptors was identified (rank order of binding affinity values: 5-CT>5-HT>5-MeOT>mesulergine approximately methiothepin>8-OH-DPAT=spiperone approximately (+)-butaclamol>>imipramine approximately (+/-)-pindolol>>ondansetron approximately clonidine approximately prazosin). 3. The autoradiographic studies revealed that the anatomical distribution of 5-HT(7) receptors throughout the human brain was heterogenous. High densities were found over the caudate and putamen nuclei, the pyramidal layer of the CA2 field of the hippocampus, the centromedial thalamic nucleus, and the dorsal raphe nucleus. The inner layer of the frontal cortex, the dentate gyrus of the hippocampus, the subthalamic nucleus and superior colliculus, among others, presented intermediate concentrations of 5-HT(7) receptors. A similar brain anatomical distribution of 5-HT(7) receptors was observed in all three mammalian species studied. 4. By using [(3)H]mesulergine, we have mapped for the first time the anatomical distribution of 5-HT(7) receptors in the human brain, overcoming the limitations previously found in radiometric studies with other radioligands, and also revisiting the distribution in guinea-pig and rat brain.

SUBMITTER: Martin-Cora FJ

PROVIDER: S-EPMC1574165 | biostudies-other | 2004 Jan

REPOSITORIES: biostudies-other

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Autoradiographic distribution of 5-HT7 receptors in the human brain using [3H]mesulergine: comparison to other mammalian species.

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