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Abstract
The present study intends to investigate the effect of lithium (Li) and celecoxib (Cel) coadministration on the behavioral status and oxidative stress parameters in a rat model of mania induced by dextroamphetamine (d-AMPH). Male Wistar rats were treated with d-AMPH or saline (Sal) for 14 days; on the 8th day of treatment, rats received lithium (Li), celecoxib (Cel), Li plus Cel, or water until day 14. Levels of oxidative stress parameters were evaluated in the serum, frontal cortex, and hippocampus. d-AMPH administration induced hyperlocomotion in rats, which was significantly reversed by Li and Cel coadministration. In addition, d-AMPH administration induced damage to proteins and lipids in the frontal cortex and hippocampus of rats. All these impairments were reversed by treatment with Li and/or Cel, in a way dependent on cerebral area and biochemical analysis. Li and Cel coadministration reversed the d-AMPH-induced decrease in catalase activity in cerebral structures. The activity of glutathione peroxidase was decreased in the frontal cortex of animals receiving d-AMPH, and treatment with Li, Cel, or a combination thereof reversed this alteration in this structure. Overall, data indicate hyperlocomotion and alteration in oxidative stress biomarkers in the cerebral structures of rats receiving d-AMPH. Li and Cel coadministration can mitigate these modifications, comprising a potential novel approach for BD therapy.
Highlights
Bipolar disorder (BD) is a prominent, impactful psychiatric disorder affecting moods, whose lifetime prevalence is ~ 5%1,2
Significant decreases in the carbonyl content were detected in the frontal cortex of rats submitted to the model of mania that received Cel; carbonyl levels in this group remained higher than those detected in the Sal + water group animals
Administration Li plus Cel to the animals submitted to the model of mania (d-AMPH + Li + Cel group) reversed the increase in the carbonyl content induced by d-AMPH in the hippocampus
Summary
Bipolar disorder (BD) is a prominent, impactful psychiatric disorder affecting moods, whose lifetime prevalence is ~ 5%1,2. The clinical hallmark of BD is the manic episodes, including euphoria, hyperactivity, insomnia, or hypersexuality, so that animal models able to reproduce mania are one of the experimental resources most used in BD research[5,6]. In this scenario, hyperlocomotion, altered pattern of sleep, and risk behavior were observed in the animal model of mania induced by amphetamine[7,8,9]. The main limitations of the mania model induced by dextroamphetamine (d-AMPH)
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