Coadministration of lithium and celecoxib reverses manic-like behavior and decreases oxidative stress in a dopaminergic model of mania induced in rats

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.

Transcriptome Changes in Three Brain Regions during Chronic Lithium Administration in the Rat Models of Mania and Depression

“…Moreover, these behaviors were reversed by the administration of mood stabilizers, including lithium [ 40 , 43 ]. This chronic amphetamine-induced mania model showed recently good face, predictive and construct validity in modeling mania in Wistar rats [ 44 , 45 , 46 , 47 ].…”

Low-dose cyclooxygenase-2 (COX-2) inhibitor celecoxib plays a protective role in the rat model of neonatal necrotizing enterocolitis

“…In this study, we also found that 0.5 mg/kg, 1 mg/kg and 1.5 mg/kg celecoxib mitigated oxidative stress in the ileum in NEC rats, accompanied by reductions in TOS and MDA, as well as increases in TAS, SOD and GPx, indicating that celecoxib alleviates oxidative stress to slow the development of NEC in rats. The potential mechanisms involved in the antioxidant activity of celecoxib include modulation of the inducible nitric oxide synthase pathway and a decrease in the generation of hydroxyl radicals [ 45 ].…”

Depressive-Like Behavior Induced by Long-Term Ouabain Administration Accompanied Alteration in Neuroinflammation Parameters in Rats

“…40 Additionally, the use of anti-in ammatory drugs as adjunctive therapy to mood stabilizers in the context of bipolar mania has demonstrated promising outcomes. 35,37,41 Accordingly, it will be of great interest that a BD animal model, besides mimic the behavioral alterations of the disorder, also recapitulates the in ammatory alterations that may occur in bipolar patients, which highlights the need for further research in this eld.…”