Binding interactions of lysergic acid diethylamide and related agents with dopamine receptors in the brain

In most brain regions saturable binding of d [³H]lysergic acid diethylamide ([³H]LSD) appears to involve postsynaptic serotonin receptors. In calf caudate, however, a portion of [³H]LSD binding involves postsynaptic dopamine receptors. Thus, in the hippocampus of calf brain, dopamine competes for [³H]LSD binding sites with a single low-affinity component, while in the caudate dopamine competition for [³H]LSD binding displays both high and low affinity components. The high affinity component, accounting for 15 to 20% of [³H]LSD binding, displays a K(i) value for dopamine of about 30nM, similar to the K(D) for the binding of [³H]dopamine itself to postsynaptic dopamine receptors in the calf caudate. Addition of serotonin to the incubations increases the proportion of [³H]LSD binding in the caudate competed for by dopamine with high affinity, presumably by occupying serotonin receptors. d LSD competes stereospecifically for [³H]dopamine binding in the caudate, consistent with the conclusion that LSD binds to dopamine receptors. Of numerous serotonin agonists and antagonists examined, several ergot alkaloids have high affinity for [³H]dopamine receptor binding in calf caudate, with K(i) values similar to that of d LSD.