Zinc deficiency alters responsiveness to antidepressant drugs in mice

Abstract

Abstract:Background: There is some evidence coming from preclinical and clinical studies suggesting a relationship between dietary zinc intake and depressive symptoms. The aim of the study was to determine whether zinc deficiency alters the response to antidepressants with a different mechanism of action. We examine also whether these changes are related to activity of the hypothalamic-pituitaryadrenal HPA axis. Methods: Male CD-1 mice were assigned to groups according to diet and antidepressant administration. To evaluate animal behavior, the immobility time in the forced swim test (FST) and locomotor activity were measured. To determine serum zinc levels the flame atomic absorption spectroscopy (FAAS) was used. The serum corticosterone was determined by radioimmunoassay (RIA). Results: Antidepressants administered to zinc-deprived mice induced an altered response in the FST when compared to animals fed with an adequate diet. There were no changes in locomotor activity. Animals subjected to a zinc-deficient diet showed a significant reduction in serum zinc levels, which was normalized by antidepressant treatment. An increase in serum corticosterone concentrations in mice fed with a zinc-deficient diet and treated with antidepressants was observed, so it can be concluded that reduced levels of zinc contribute hyperactivation of the HPA axis. Conclusion:The results of this study suggest that a diet with a reduced zinc level alters antidepressant action, which is associated with a reduction in the serum zinc level and rise in the corticosterone level. The results of this study may indicate the involvement of zinc deficiency in the pathogenesis of depression.

Relationship of Zinc and Magnesium Serum Levels with Postpartum Depression in Tabriz-Iran

“…In some studies, including a meta-analysis, zinc serum level in depressive patients was lower than non-depressive individuals (DiGirolamo & Ramirez-Zea, 2009;Mlyniec et al, 2013;Siwek et al, 2013;Swardfager et al, 2013). Thus, low serum zinc concentrations may have a role in the pathogenesis of depression.…”

“…However, some other studies have not suggested any statistically significant relationship between the zinc and magnesium serum levels with depression (Crayton & Walsh, 2007;Islam et al, 2013). The anti-depression feature of zinc and magnesium has been seen in animal studies, including on mice (Kroczka et al, 2001;Mlyniec et al, 2013;Samardzic et al, 2013;Poleszak et al, 2004). This study aims at determining the relationship between zinc and magnesium serum levels with PPD before the development of its severe symptoms and signs, as an assumed cause of PPD, to find a prevention method by keeping serum level high, in case of such relationship.…”

Zinc in the Monoaminergic Theory of Depression: Its Relationship to Neural Plasticity

“…Chronic administration of the zinc-deficient diet was found to alter the responsiveness to antidepressant drugs [65]. Animals subjected to a zinc-deficient diet and treated with an acute injection of escitalopram or imipramine displayed increased immobility time in the FST, compared to animals treated with a zinc-adequate diet and the respective antidepressant agent [65].…”

“…Animals subjected to a zinc-deficient diet and treated with an acute injection of escitalopram or imipramine displayed increased immobility time in the FST, compared to animals treated with a zinc-adequate diet and the respective antidepressant agent [65]. Additionally, increased immobility time was observed in mice that received a zinc-deficient diet and chronic treatment with escitalopram, compared to mice that received a zinc-adequate diet and the drug, whereas chronic imipramine treatment did not result in such differences between the zinc-deficient and zinc-adequate rats [65]. Chronic dietary deprivation of zinc produces a depressive- and anxiety-like phenotype [22–24, 66, 67].…”

Nutritional psychiatry research: an emerging discipline and its intersection with global urbanization, environmental challenges and the evolutionary mismatch

“…Zinc provides a good example. The results of a number of preclinical and clinical studies have indicated that zinc supplementation may be helpful for people with major depression [91], and low dietary zinc has not only been correlated with depression [92], but has also been linked to abnormalities in the response to antidepressant medication [93]. However, zinc is well-established to play key roles in the metabolism of ω-3 and other essential fatty acids [94].…”