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Molecular Pharmacology, Vol 12, 631-638, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Binding Interactions of Lysergic Acid Diethylamide and Related Agents with Dopamine Receptors in the Brain

DAVID R. BURT 1, IAN CREESE 1, and SOLOMON H. SNYDER 1

1 Departments of Pharmacology and Experimental Therapeutics and of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

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.

Note:
ACKNOWLEDGMENTS We thank Janet Ryan for excellent technical assistance.

Submitted on December 10, 1975




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Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics