Depression and anxiety are common psychiatric disorders accounting for social and economic burdens. Previous studies have shown that oxidative stress and oxidant/antioxidant imbalance are involved in the pathophysiology of psychiatric disorders. Experiencing early-life adversities (like maternal separation [MS] stress) provoked psychiatric disorders. Trigonelline (TRG) is a pyridine alkaloid that has various pharmacological effects including hypoglycemic, neuroprotective and memory-improving properties. To investigate the antidepressant-and anxiolytic-like effects of TRG focusing oxidative stress, we applied the MS paradigm to male mice at postnatal day (PND) 2-14 (3 h daily, 9-12 a.m.) and investigated the behaviors at PND 45-47. Using valid behavioral tests including a forced swimming test (FST), splash test, open field test (OFT) and elevated plus maze (EPM), we investigated behavioral modifications. Additionally, we examined the effects of MS and TRG treatment on the level of malondialdehyde (MDA), nitric oxide (NO) and also antioxidant capacity in the brain and serum. Our results showed that MS provoked depressive-and anxiety-like behaviors in the FST, OFT, EPM and splash test, which are associated with an increase in MDA and NO levels as well as a decrease in antioxidant capacity in the brain and serum samples. Findings determined that TRG significantly reversed the negative effects of MS on behavior that is accompanied by a decrease in MDA and NO as well as an increase in antioxidant capacity. Findings of the present study showed that beneficial effects of TRG may be, at least partially, mediated via the reduction of oxidative stress and an increase of antioxidant capacity.
BackgroundExperiencing early-life stress plays an important role in the pathophysiology of anxiety disorders. Ferulic acid is a phenolic compound found in some plants which has several pharmacological properties. N-methyl-D-aspartate (NMDA) receptors are involved in the pathophysiology of mood disorders. In this study we aimed to assess the anxiolytic-like effect of ferulic acid in a mouse model of maternal separation (MS) stress by focusing on the possible involvement of NMDA receptors.MethodsMice were treated with ferulic acid (5 and 40 mg/kg) alone and in combination with NMDA receptor agonist/antagonist. Valid behavioral tests were performed, including open field test (OFT) and elevated plus maze test (EPM), while quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate gene expression of NMDA subunits (GluN2A and GluN2B) in the hippocampus.ResultsFindings showed that treatment of MS mice with ferulic acid increased the time spent in the central zone of the OFT and increased both open arm time and the percent of open arm entries in the EPM. Ferulic acid reduced the expression of NMDA receptor subunit genes. We showed that administration of NMDA receptor agonist (NMDA) and antagonist (ketamine) exerted anxiogenic and anxiolytic-like effects, correspondingly. Results showed that co-administration of a sub-effective dose of ferulic acid plus ketamine potentiated the anxiolytic-like effect of ferulic acid. Furthermore, co-administration of an effective dose of ferulic acid plus NMDA receptor agonist (NMDA) attenuated the anxiolytic-like effect of ferulic acid.ConclusionsIn deduction, our findings showed that NMDA, partially at least, is involved in the anxiolytic-like effect of ferulic acid in the OFT and EPM tests.
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