LSD labels a novel dopamine receptor in molluscan nervous system

Abstract

ELECTROPHYSIOLOGICAL studies on molluscan ganglia have provided evidence for the presence of two pharmacologically distinct dopamine responses—a hyperpolarising response which is inhibited by low concentrations of ergot alkaloids and related drugs, and a depolarising response which is sensitive to neuroleptics such as haloperidol1–3. Although dopamine receptors in the mammalian central nervous system (CNS) have been detected directly by the binding of a number of 3H-labelled ligands, including the lysergic acid derivatives lysergic acid diethylamide (LSD) and dihydroergocryptine4–8, no such studies have been reported with molluscan nervous system. We report here that 3H-LSD binds to both dopamine and serotonin (5-HT) receptors in molluscan ganglia, but that conditions can be obtained which allow the two receptors to be studied separately. This is the first demonstration that dopamine and 5-HT receptors may be investigated individually in the same tissue using a single ligand. The pharmacological characteristics of the dopamine-sensitive 3H-LSD binding are compatible with the properties of the dopamine receptor which mediates hyperpolarisation in certain molluscan neurones. These receptors are, however, different from the dopamine receptors previously described in the mammalian CNS.