TY - JOUR
T1 - N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and d-amphetamine-treated rats
T2 - Relevance to schizophrenia and bipolar disorder
AU - Dean, Olivia M.
AU - Van Den Buuse, Maarten
AU - Berk, Michael
AU - Copolov, David L.
AU - Mavros, Christine
AU - Bush, Ashley I.
PY - 2011/7/25
Y1 - 2011/7/25
N2 - 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.
AB - 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.
KW - 2-Cyclohexene-1-one (CHX)
KW - Acetyl cysteine
KW - Amphetamine
KW - Bipolar disorder
KW - Glutathione
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=79960084100&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2011.05.027
DO - 10.1016/j.neulet.2011.05.027
M3 - Article
C2 - 21621586
AN - SCOPUS:79960084100
SN - 0304-3940
VL - 499
SP - 149
EP - 153
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 3
ER -