N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and d-amphetamine-treated rats: Relevance to schizophrenia and bipolar disorder

Olivia M. Dean, Maarten Van Den Buuse, Michael Berk, David L. Copolov, Christine Mavros, Ashley I. Bush

Research output: Contribution to journalArticleOtherpeer-review

74 Citations (Scopus)


Oxidative stress and reduced brain levels of glutathione have been implicated in schizophrenia and bipolar disorder. N-acetyl cysteine (NAC) is a precursor of glutathione and has additional effects on glutamate neurotransmission, neurogenesis and inflammation. While NAC treatment has shown benefits in both schizophrenia and bipolar disorder, the mechanisms of action are largely unknown. Similarly, the interaction between oxidative stress and altered dopaminergic activities in psychiatric illness is not yet characterized. This study investigated the capacity of NAC in restoring brain glutathione depletion in rats that received 2-cyclohexene-1-one (CHX, 75. mg/kg), d-amphetamine (2.5. mg/kg) or both. CHX, but not amphetamine, induced significant depletion of glutathione levels in the striatum and frontal cortex. Glutathione depletion was reversed by NAC (1000. mg/kg) in saline-treated and amphetamine-treated (frontal cortex only) rats. While NAC was shown to be beneficial in this model, the lack of additional glutathione depletion by amphetamine in combination with CHX does not support a summative interaction between oxidative stress and altered dopamine transmission.

Original languageEnglish
Pages (from-to)149-153
Number of pages5
JournalNeuroscience Letters
Issue number3
Publication statusPublished - 25 Jul 2011


  • 2-Cyclohexene-1-one (CHX)
  • Acetyl cysteine
  • Amphetamine
  • Bipolar disorder
  • Glutathione
  • Schizophrenia

Cite this