Abstract
Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX) to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing) rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.
Highlights
Stressors evoke various adaptive or maladaptive responses in individuals that may strengthen or weaken their response, respectively, to forthcoming stress in the near or distant future [1,2]
The concentration of glutathione in the nucleus accumbens (NAc) or dorsal striatum of the control animals administrated saline was approximately 30–40 nmol/mg, nearly compatible with previous reports that employed similar methods [25,26], and there was no significant difference between these two regions
Acute administration of 12.5 mg/kg CHX did not detectably reduce glutathione levels, whereas CHX doses ! 25 mg/kg induced a significant reduction in total glutathione levels in the NAc, confirming a dose-dependent effect of CHX on total glutathione levels
Summary
Stressors evoke various adaptive or maladaptive responses in individuals that may strengthen or weaken their response, respectively, to forthcoming stress in the near or distant future [1,2]. Many psychiatric disorders of humans, such as schizophrenia, major depression, posttraumatic stress disorder, and drug addiction, can be triggered, reversed, or exacerbated when there is unexpected excessive exposure to diverse stressors or when individuals are vulnerable to these stressors [3,4,5]. Oxidative Stress Affects Neural Functions in Adult Rats and analysis, decision to publish, or preparation of the manuscript
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