Serotonin and lysergic acid diethylamide binding in rat brain membranes. Relationship to postsynaptic serotonin receptors

[³H] Serotonin (5 HT) binds to membrane preparations of rat brain in a saturable fashion and with substrate specificity and regional variations consistent with its binding to the postsynaptic serotonin receptor. The dissociation constant for [³H]5 HT binding is about 8 nM, and the total number of 5 HT binding sites in the brain is 16 pmoles/g of tissue, wet wt. There is considerable structural specificity in the affinity of various tryptamines for the [³H]5 HT binding sites, with a crucial role played by the 5 hydroxy substituent. d [³H]Lysergic acid diethylamide (LSD) binding sites have substrate specificity requirements similar to the [³H]5 HT binding sites, but the 5 hydroxy substituent is less critical. 5 HT and related agonists have about 100 times more affinity for 5 HT than LSD binding sites, while classical 5 HT antagonists have 4 to 100 times greater affinity for LSD binding sites. LSD itself has a similar affinity for 5 HT and LSD binding sites. Raphe lesions which result in degeneration of 5 HT neurons do not lower [³H]5 HT binding, indicating that binding does not take place to presynaptic 5 HT neurons. Regional variations in serotonin and LSD binding are fairly similar. Highest binding occurs in the corpus striatum, hippocampus, and cerebral cortex, with lowest binding in the cerebellum. The ontogeny of 5 HT and LSD binding sites is nearly identical and does not appear to depend on functionally intact presynaptic 5 HT neuronal input.