NEUROTROPHIC EFFECTS OF L-DOPA IN POSTNATAL MIDBRAIN DOPAMINE NEURON CORTICAL ASTROCYTE COCULTURES

L-DOPA is toxic to catecholamine neurons in culture, but the toxicity is reduced by exposure to astrocytes. We tested the effect of L-DOPA o n dopamine neurons using postnatal ventral midbrain neuron/cortical as trocyte cocultures in serum-free, glia-conditioned medium. L-DOPA (50 mu M) protected against dopamine neuronal cell death and increased the number and branching of dopamine processes. In contrast to embryonica lly derived glia-free cultures, where L-DOPA is toxic, postnatal midbr ain cultures did not show toxicity at 200 mu M L-DOPA. The stereoisome r D-DOPA (50-400 mu M) was not neurotrophic. The aromatic amino acid d ecarboxylase inhibitor carbidopa (25 mu M) did not block the neurotrop hic effect. These data suggest that the neurotrophic effect of L-DOPA is stereospecific but independent of the production of dopamine. Howev er, L-DOPA increased the level of glutathione. Inhibition of glutathio ne peroxidase by L-buthionine sulfoximine (3 mu M for 24 h) blocked th e neurotrophic action of L-DOPA. N-Acetyl-L-cysteine (250 mu M for 48 h), which promotes glutathione synthesis, had a neurotrophic effect si milar to that of L-DOPA. These data suggest that the neurotrophic effe ct of L-DOPA may be mediated, at least in part, by elevation of glutat hione content.