Multiple serotonin receptors: regional distribution and effect of Raphe lesions

These studies confirm and extend the recent work suggesting that [3H]lysergic acid diethylamide (LSD) labels two distinct binding sites in rat brain resembling serotonin (5HT) receptors. Although Scatchard analyses of [3H]LSD binding to membranes prepared from cortex/hippocampus were linear, the heterogeneity of the [3H]LSD binding sites was clearly demonstrated in displacement studies. The displacement curves for both 5HT and spiperone were bisigmoidal with the concentration required to saturate the high affinity components nearly 3 orders of magnitude lower than the concentration necessary to saturate the low affinity components. Additivity studies suggested that the sites with high affinity for 5HT and spiperone are different, independent sites. These sites are referred to as 5HT, and 5HT2, respectively. Regional analyses showed, that in the frontal cortex, the density of the 5HT2 site was slightly greater than the 5HT1 site, whereas the 5HT1 site was predominant in all other brain areas, including the spinal cord. The pharmacological properties of the two sites have features in common with 5HT receptors; however, electrolytic lesions of the midbrain raphe nuclei did not change the densities or binding constants of the two apparent 5HT receptor subtypes, even though the number of high affinity 5HT uptake sites was markedly reduced.