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

TLDR: 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 displays both high- and low affinity components as mentioned in this paper.

Abstract: 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 15-20% of [3H]LSD binding, displays a Ki value for dopamine of about 30 nM, similar to the KD 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 Ki values similar to that of d -LSD. ACKNOWLEDGMENTS We thank Janet Ryan for excellent technical assistance.