Abstract
Depressive disorder is a recurrent illness that affects large numbers of the general population worldwide. In recent years, the goal of depression treatment has moved from symptomatic response to that of full remission. However, treatment-resistant depression is a major challenge in the treatment of depression or depression-related disorders. Consensus opinion, therefore, suggests that effective combined aggressive initial treatment is the most appropriate strategy. This study aimed to evaluate the effects of quercetin (QUR) and/or ascorbic acid (AA) on Phenobarbital-induced sleeping mice. QUR (50 mg/kg) and/or AA (25 mg/kg) with or without intraperitoneally pre-treated with GABA receptor agonist (diazepam: 2 mg/kg, i.p.) or antagonist (Flumazenil: 2.5 mg/kg, i.p.) to underscore the effects, as well as the possible involvement of the GABA receptor in the modulatory action of QUR and AA in sleeping mice. Additionally, an in silico study was undertaken to predict the involvement of GABA receptors in the sleep mechanism. Findings suggest that the pretreatment of QUR and AA modulated the onset and duration of action of the standard drugs in experimental animals. The acute administration of QUR and/or AA significantly (p < 0.05) reversed the DZP-mediated onset of action and slightly reversed the duration of sleep time in comparison to the vehicle (control) group. A further combination of QUR or AA with the FLU resulted in an enhancement of the onset of action while reducing the duration of action, suggesting a FLU-like effect on the test animals. In in silico studies, AA and QUR showed good to moderate binding affinities with GABAA and GABAB receptors. Both QUR and AA produced a stimulatory-like effect on mice, possibly through the GABAA and GABAB receptor interaction pathways. Further studies are necessary to verify this activity and clarify the exact mechanism of action(s) involved.
Highlights
There are several situations and conditions that stimulate stress to vary degrees in humans [1]
A pretreatment of ascorbic acid (AA)-plus QUR was found to reduce the latency period significantly (p < 0.05) in the DZP group when compared to the QUR and AA groups
This study demonstrated that when QUR and/or AA are co-administered, they may interact with GABAA and GABAB activation and produce a modulatory effect in the mouse experimental model
Summary
There are several situations and conditions that stimulate stress to vary degrees in humans [1]. It is estimated that major depressive disorders are expected to be the primary cause of disability in the world by 2030. These disorders are currently considered the most common psychiatric illnesses affecting humans [3]. These are associated with significant disability, socioeconomic burden, and a negative impact on the quality of life [4]. For producing anxiolytic and/or antidepressant drugs, the gammaaminobutyric acid (GABA) receptor is the most essential target [7]. At the pharmacological and molecular level, the GABA receptor has two subtypes—GABAA , and GABAB [8]
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