Haloperidol treatment after high-dose methamphetamine administration is excitotoxic to GABA cells in the substantia nigra pars reticulata

Theo Hatzipetros, Jamie G. Raudensky, Jean Jacques Soghomonian, Bryan K. Yamamoto

Research output: Contribution to journalArticle

14 Scopus citations


The therapeutic management of methamphetamine (METH)-induced psychoses often involves treatment with the typical antipsychotic drug and dopamine D 2 receptor antagonist haloperidol. We report here that subchronic haloperidol administration after a high-dose regimen of METH produces a heretofore unrecognized toxicity to GABAergic cells, as reflected by GAD67 mRNA expression histochemistry, in the rat substantia nigra pars reticulata (SNr) through an acute and persistent augmentation of glutamate release, NMDA receptor activation, and DNA fragmentation. The dopaminergic cells in the substantia nigra pars compacta were unaffected by METH or haloperidol alone or the combination of METH and haloperidol. These findings suggest that the current therapeutic management of METH-induced psychoses with haloperidolmaybe contraindicated because of a resultant GABAergic cell death in the SNr, which may predispose some individuals to the development of hyperkinetic movement disorders and seizures.

Original languageEnglish (US)
Pages (from-to)5895-5902
Number of pages8
JournalJournal of Neuroscience
Issue number22
StatePublished - May 30 2007



  • Antipsychotics
  • Basal ganglia
  • Dopamine
  • Glutamate
  • Microdialysis
  • Neurodegeneration

ASJC Scopus subject areas

  • Neuroscience(all)

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