5-HT_1C, 5-HT_1D and 5-HT₂ Receptors in Mammalian Brain: Multiple Affinity States with a Different Regional Distribution

Summary

In vitro ligand binding autoradiography was used to:

• investigate regional differences in the sensitivity of 5-HT_1D/5-HT_1B binding sites to the agonist 5-carboxamidotryptamine (5-CT),

• compare the distribution of 5-HT_1C sites labelled by [³H]5-HT, [¹²⁵I]DOI or by [³H]mesulergine,

• compare the distribution of 5-HT₂ sites labelled by [¹²⁵I]DOI, [³H]LSD or [³H]ketanserin.

The data show that 5-CT competes for 5-HT_1D binding sites with a biphasic profile. In rat, guinea-pig and human brain, the proportion of sites with a high affinity for 5-CT is higher in the substantia nigra and globus pallidus than in the caudate/putamen and the cortex. These studies also demonstrate that antagonist ligands reveal a more widespread distribution of 5-HT _lCand 5-HT₂ sites than agonist ligands, indicating that these receptors might exist in multiple affinity states with different regional distributions.