Zingerone neuroprotective effects in a rat model of manic-like behavior induced by ketamine

• Published in: Learning and motivation Vol. 84; p. 101934
• Main Authors: Maleki, Mahsa, Moosavi, Mehrnoosh, Zeidooni, Leila, Azadnasab, Reza, Khodayar, Mohammad Javad
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2023
• Subjects: Inflammation; Ketamine; Mania; Oxidative stress; Rat; Zingerone; NO; Oxidative stress; BD; LiCl; MLB; AJUMS; RNA; ZGR; Rat; HLM; mRNA; H2O2; PFC; Zingerone; BSA; SH; NMDA; iNOS; OS; SOD; i.p; TBARS; Inflammation; NIH; IL-1β; IL-6; p.o; Ketamine; TNF-α; CAT; ROS; Mania; HPC; SEM; KET
• ISSN: 0023-9690; 1095-9122
• DOI: 10.1016/j.lmot.2023.101934

Bipolar disorder (BD), before known as manic depression, is a chronic illness and a mood disorder characterized by manic and depressive periods. Drugs used to treat bipolar disorder can cause side effects if used chronically. Therefore, new therapeutic approaches are needed for treatment of BD. Given that inflammatory parameters and oxidative markers increase in BD and on the other hand there are a lot of evidences that zingerone (ZGR) has antioxidant and anti-inflammatory effects, the aim of this study was to investigate the neuroprotective effects of ZGR as one of the active phytochemicals existing in ginger in a model of manic-like behavior (MLB) induced by ketamine (KET) in rats. Thirty-six rats were randomly divided into six groups, including three groups of healthy rats: control, lithium chloride (LiCl) (45 mg/kg, p.o.) and ZGR (50 mg/kg, p.o.), and three groups of MLB rats (received 25 mg/kg KET, i.p. from day 8 to day 15): control, lithium (45 mg/kg, p.o.) and ZGR (50 mg/kg, p.o.). Pre-treatment with ZGR (50 mg/kg) once daily or LiCl (45 mg/kg) twice a day for 14 days prevented all KET-induced changes except total sulfhydryl content (total SH), which was not significant. The data of this study showed that 25 mg/kg KET increased the number of crossings in the open-field test and induced oxidative and inflammatory damage in the rat hippocampus (HPC) and prefrontal cortex (PFC). KET increased thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), and tumor necrosis factor-alpha (TNF-α) levels; and decreased the activity of catalase (CAT) and superoxide dismutase (SOD) enzymes as well as the amount total SH in the HPC and PFC. These findings suggest that oxidative stress (OS) and inflammation may play an important role in BD, and ZGR as an anti-inflammatory and antioxidant agent might be able to reduce the oxidative and inflammatory damage related to the manic phase of this disorder. [Display omitted] •Ketamine in repeated sub-anesthetic doses induced manic-like behavior.•Zingerone had neuroprotective effects in manic-like behavior induced by ketamine.•Zingerone decreased locomotion, oxidative stress, and inflammation.•Zingerone can be suggested as an anti-manic to reduce manic episode fluctuations.