Synergistic Action of Sodium Selenite with some Antidepressants and Diazepam in Mice.

Ewa Kędzierska,Ewa Poleszak,Piotr Wlaź,Jolanta Kotlińska,Paweł Obierzyński,Magdalena Polakowska,Katarzyna Szewczyk,Lila Dąbkowska

doi:10.3390/pharmaceutics10040270

Abstract

Background: The antidepressant and anxiolytic effects of selenium (Se) have been proven in many studies. This work was aimed at confirming these activities of its inorganic form—sodium selenite—and examining the possible synergy of action with antidepressants and diazepam. Methods: The antidepressant- and anxiolytic-like activity of Se was assessed using forced swim tests (FSTs) and elevated plus-maze test (EPMs). Spontaneous locomotor activity was measured using photoresistor actimeters. The experiments were conducted on male Albino Swiss mice. Results: Sodium selenite (0.5 mg/kg) reduced the immobility time in the FSTs and extended time spent in the open arms of EPMs without affecting locomotor activity The combined administration of Se at an ineffective dose (0.25 mg/kg) together with imipramine (15 mg/kg), fluoxetine (5 mg/kg), tianeptine (10 mg/kg), but not with reboxetine (2.5 mg/kg), resulted in a reduction of immobility time in FSTs, and with a threshold dose of diazepam (0.25 mg/kg) led to the prolongation of time spent in the open arms of the EPM. Moreover, the antidepressant-like effect of Se (0.5 mg/kg) was significantly reduced by pretreatment with p-chlorophenylalanine (100 mg/kg). Conclusions: The results may indicate the participation of serotonergic transmission to antidepressant action of Se and GABA-ergic transmission to its anxiolytic effects.

Highlights

Depression is a common mental illness that leads to mental impairment, physical disability, and socioeconomic burden [1]
Current hypotheses regarding the etiology of the depressive disorder tend to integrate monoaminergic, neuroendocrine, and immunological concepts with those based on oxidative stress, neuronal plasticity, and neurogenesis disturbances
Sodium selenite was tested in the forced swim tests (FSTs) and elevated plus-maze test (EPMs) tests, which are well-known behavioral procedures [35,36,37]

Summary

Introduction

Depression is a common mental illness that leads to mental impairment, physical disability, and socioeconomic burden [1] It is one of the most widespread psychiatric disorder in the world, estimated to affect up to 21% of the population, and according to World Health Organization (WHO) predictions, it will be the second most frequently occurring disease in 2020 [2]. Many research papers highlight the involvement of several pathways i.e., serum lipids, hypothalamic–pituitary–adrenal axis (HPA axis), inflammatory system, gut microbiota, kynurenine pathway [5,6,7,8,9,10,11,12,13] This complexity of various factor interactions may be the cause of increased risk of atherosclerosis and cardiovascular changes such as ischemic heart disease [14] and stroke [15] as well as endocrine dysregulation [16]. Conclusions: The results may indicate the participation of serotonergic transmission to antidepressant action of Se and GABA-ergic transmission to its anxiolytic effects

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