Platelet Serotonin (5-HT)2A Receptor Binding Sites in Affective Disorders: A Quantitative Receptor Autoradiographic Study with [ 125I ] Lysergic Acid Diethylamide

We used the quantitative receptor autoradiographic method with a radioligand of [ 125I ]lysergic acid diethylamide ([125I]LSD) to quantitate platelet serotonin (5-HT)2A receptors in affective disorders. Specific binding of [125I]LSD to human platelet pellet sections was saturable, and of high affinity and single. Both ketanserin and spiperone, 5-HT2A selective ligands, inhibited [125I]LSD binding to human plate-let pellets with high potency (IC50 values of 0.15 and 0.19 nM, respectively), whereas 5-HT and paroxetine, selective 5-HT re-uptake inhibitors, inhibited binding with a very low potency. These data confirmed that binding sites of human plate-let pellets specifically labelled by [125I] LSD were 5-HT2A receptors. The number of 5-HT2A receptors (Bmax of [ 125I] LSD binding) of human platelets obtained from drug-free depressed patients was significantly higher than those of healthy volunteers. There were no statistical differences in the number of 5-HT2A receptors between depressed patients with and without suicidal behaviors. The increased number in platelet 5-HT2A receptotrs may indicate a hyperfunction of the central 5-HT2A receptors. The method with human platelets pellet sections we used is simple and sensitive for investigating platelet 5-HT2A receptors, a diagnostic and therapeutic marker in depressive disorders, in the clinical research.