Dopamine Protects Neurons against Glutamate-Induced Excitotoxicity

Abstract—

Parkinson’s disease is associated with neuronal loss in the midbrain and the resulting development of dopamine-deficient states. At the later stages of the disease, increased neuronal death is also observed in other parts of the brain. We hypothesized that dopamine may function as a glutamate antagonist, and dopamine deficiency may increase glutamate-induced excitotoxicity. Using rat hippocampal primary culture and fluorescence microscopy, we show that dopamine reduces the amplitude of calcium response evoked by the activation of NMDA receptors but does not affect calcium signals mediated by AMPA and KA receptors. Voltage-gated calcium channels are also unaffected by dopamine. It was shown that the effect of dopamine depends not only on NMDA receptors, but also on D2-type dopamine receptors and on GABA(A) receptor. Dopamine reduced glutamate-induced mitochondrial depolarization and improved neuronal survival in the presence of toxic levels of glutamate. The data presented suggest a protective role of dopamine against glutamate toxicity.