Autoradiographic analysis of 5-HT receptor subtypes labeled by [3H]5-CT ([3H]5-carboxamidotryptamine)

This work examines the autoradiographic distribution of serotonin (5-HT) receptor subtypes in rat, guinea pig and human brain, using [3H]5-HT and [3H]5-CT as ligands. Different displacers were used to mask radioligand binding to 5-HT1A, 5-HT1B/1D and 5-HT2C receptors, in an attempt to visualize other receptor populations, which presumably would correspond to 5-HT1E and 5-HT1F sites. Brain areas enriched in 5-HTnon1A/1B/1D sites in guinea pig were the hilus, dentate gyrus, striatum, claustrum, substantia nigra and superior colliculus, among others. In humans, however, the claustrum, a structure supposed to contain 5-HT1E sites, showed significant densities of [3H]5-CT binding. An interesting finding was that blockade [3H]5-CT binding to 5-HT1A receptors by 8-OH-DPAT could only be achieved at very high concentrations of the displacer. This could be due to differences in the affinity of ligands in intact tissue sections compared to membrane homogenates or cell lines. Another possibility would be that [3H]5-CT labels 5-HT1A receptors in the low-affinity state. These hypotheses remain to be investigated.