Multiple Serotonin Receptors: Differential Binding of [3H]5-Hydroxytryptamine, [3H]Lysergic Acid Diethylamide and [3H]Spiroperidol

TLDR

Radiolabeled serotonin, LSD, and spiroperidol bind selectively to rat frontal cortex membranes, indicating distinct serotonin receptor interactions. The study proposes that radiolabeled 5‑HT and spiroperidol label separate serotonin receptor populations (5‑HT1 and 5‑HT2) in rat brain. Differential competition experiments show that 5‑HT and spiroperidol bind distinct receptor populations, whereas LSD binds both, with binding specificity shifting depending on pre‑incubation with either ligand.

Abstract

[3H]5-Hydroxytryptamine (5-HT), [3H]lysergic acid diethylamide (LSD) and [3H]spiroperidol bind to membranes from the rat frontal cerebral cortex in a manner indicating a selective interaction with serotonin receptors. Differential drug potencies in competing for [3H]5-HT and [3H]spiroperidol binding sites suggest that these two [3H]ligands respectively label two distinct populations of receptors, while [3H]LSD labels both the [3H]5-HT and [3H]spiroperidol sites. After incubation of brain membranes with 30 nM spiroperidol, drug specificity of the residual [3H]LSD binding resembles that of receptors labeled by [3H]5-HT. Conversely, drug effects on [3H]LSD binding in the presence of 300 nM 5-HT resemble effects with [3H]spiroperidol. We propose that [3H]5-HT and [3H]-spiroperidol label distinct populations of serotonin receptors in rat brain, designated 5-HT1 and 5-HT2 receptors, respectively. [3H]LSD appears to bind to both receptors to a similar extent.