Multiple serotonin receptors: Differential binding of [³H]5-hydroxytryptamine, [³H]lysergic acid diethylamide and [³H]spiroperidol

[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 resembles 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.