title: N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and d-amphetamine-treated rats: relevance to schizophrenia and bipolar disorder.
abstract: 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 (2.5mg/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.
authors.affiliation: The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia. oliviad@barwonhealth.org.au
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Dean
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: David L
authors.initials: DL
authors.lastname: Copolov
authors.forename: Christine
authors.initials: C
authors.lastname: Mavros
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001714:Bipolar Disorder / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003512:Cyclohexanones / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000378:metabolism*
chemical_list: D003512:Cyclohexanones; C028215:2-cyclohexen-1-one; D005978:Glutathione; D003913:Dextroamphetamine; D000111:Acetylcysteine