Responses of rat substantia nigra compacta neurones to L-DOPA

1. The electrophysiological actions of L-DOPA were studied on substantia nigra dopamine-containing neurones by use of intracellular recordings, current and voltage clamp, in vitro. 2. L-DOPA (3-300 microM), applied by superfusion, decreased the spontaneous firing activity of the neurones, hyperpolarized the membrane potential and produced an outward current. 3. These effects of L-DOPA were graded and were antagonized by sulpiride, a D2-receptor antagonist. 4. The L-DOPA activated membrane hyperpolarization persisted in slices exposed to tetrodotoxin while it was markedly reduced or abolished in solutions with no calcium plus cobalt (2 mM). 5. In slices treated with carbidopa, an inhibitor of the aromatic amino acid decarboxylase enzyme, the actions of L-DOPA were greatly reduced. 6. We propose that L-DOPA inhibits the firing of substantia nigra zona compacta neurones by being converted to dopamine which is then released by these cells.