Dopamine neurotoxicity in cortical neurons

Sudarkodi Alagarsamy, Melissa Phillips, Todd Pappas, Kenneth M. Johnson

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Dopamine (DA), at concentrations greater than 100 μM, has previously been demonstrated to be toxic to mesencephalic, striatal and dorsal root ganglion cell cultures. Pharmacological experiments suggest that DA also may play a role in the cortical neurotoxicity caused by systemic administration of N-methyl-D-aspartate receptor antagonists such as phencyclidine and MK-801. In this study, the potential toxicity of DA in primary cortical cell cultures was determined in vitro. Using calcein and ethidium homodimer fluorescence as a marker for live and dead cells, respectively, we observed that a 24 h treatment with 10-100 μM DA produced a concentration-dependent increase in the number of ethidium homodimer-labelled cells. The cell death induced by 10 μM DA was dramatically reduced by co-administration of either superoxide dismutase and catalase or deferoxamine mesylate, an iron chelator. To verify this observation, the effects of 10 μM DA on the release of cytoplasmic lactate dehydrogenase (LDH) was measured. DA increased LDH release in a manner that was inhibited by both superoxide dismutase/catalase and deferoxamine. Nomifensine potentiated the effect of DA on LDH release, suggesting a protective role for DA uptake in this system. On the other hand, neither D1 nor D2 antagonists were able to prevent DA-induced LDH release. These data suggest that relatively low concentrations of DA can be injurious to cortical neurons through a mechanism that likely involves DA autooxidation and the formation of reactive oxygen species such as superoxide anion and hydroxyl radical. This mechanism may be important in the toxic effects of psychomotor stimulants such as amphetamine. However, the failure of DA receptor antagonists to affect DA-induced injury argues that the effect of DA on cortical neurons in culture does not model the toxic effect of phencyclidine and MK-801 observed in vivo.

Original languageEnglish (US)
Pages (from-to)105-111
Number of pages7
JournalDrug and Alcohol Dependence
Issue number2
StatePublished - Nov 25 1997
Externally publishedYes


  • Cortical cells
  • Dopamine neurotoxicity
  • Dopamine receptor antagonists
  • NMDA antagonists

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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