Binding sites for 5-hydroxytryptamine-2 receptor agonists are predominantly located in striosomes in the human basal ganglia.

Previous autoradiographic studies have shown that serotonin 5-HT2 receptors are homogeneously distributed in the human striatum. While these studies were done using antagonist radioligands such as [3H]ketanserin, we describe here a heterogeneous distribution of 5-HT2 binding sites in the human striatum, using [3H]LSD and [125I]DOI as ligands. Beside their agonist properties, these compounds belong to the family of psychedelic drugs. The localization of their binding sites in the dorsal striatum is very similar to that of striosomes, as visualized by acetylcholinesterase histochemistry or [3H]flunitrazepam labelling. This heterogeneous distribution seems to be a peculiarity of the human and guinea-pig brain, for it is not found in the monkey, cat, pig, and cow. In the rat striatum, a weak patchniness was seen, but corresponded to 5-HT1C binding sites. The density of [125I]DOI binding sites over striosomes presents large variations, which can neither be correlated with parameters such as age, gender and post-mortem delay nor with the effects of neurodegenerative disorders, with the exception of Huntington's disease, at late stages of the disease. The drug binding profile of [125I]DOI binding sites in the striosomes is identical to that of matrix binding sites. It is also fully comparable to the pharmacological profile of cortical 5-HT2 sites reported using [3H]ketanserin as a radioligand, with the exception of the higher affinity displayed by agonists for [125I]DOI binding sites. Interestingly, biphasic displacement curves yield a better fit for spiperone, cinanserin and ketanserin competitions. This biphasic profile can probably neither be accounted for by the presence of 5-HT1C sites nor by the existence of multiple affinity states. Taken together, these data suggest that a heterogeneous population of 5-HT2 receptors is present on the cell bodies or dendrites of striosomal neurons. These receptors provide an additional anatomical substrate to explain the psychedelic action of indoleamine (LSD) and phenylethylamine (DOI, DOM) drugs.