Antidepressant activity of fluoxetine in the zinc deficiency model in rats involves the NMDA receptor complex

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

“…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]. Chronic administration of fluoxetine to the zinc-deficient rats resulted in the normalization of depressive-like behavior induced by the diet, as measured by decreased immobility time in the FST [66].…”

“…Chronic dietary deprivation of zinc produces a depressive- and anxiety-like phenotype [22–24, 66, 67]. Chronic administration of fluoxetine to the zinc-deficient rats resulted in the normalization of depressive-like behavior induced by the diet, as measured by decreased immobility time in the FST [66]. On the contrary, Tassabehji et al [25] did not observe a significant reduction in the immobility time in the zinc-deficient rats treated with fluoxetine, compared to zinc-deficient rats that did not receive the antidepressant.…”

“…This finding may have resulted from different study design. In the study of Doboszewska et al [66] the rats received the zinc-deficient diet for 4 weeks (i.e., for a period of time after which behavioral (increased immobility time in the FST, anhedonia) and neurobiological changes associated with depression are established [27]) and for subsequent 2 weeks they received fluoxetine (10 mg/kg/day intraperitoneally (i.p.)) in addition to the diet, whereas in the study of Tassabehji et al [25] the rats received the zinc-deficient diet and fluoxetine (10 mg/kg/day via drinking water) for 3 weeks.…”

“…It should be noted that Tassabehji et al [25] observed anhedonia, which is one of the core symptoms of depression, in the zinc-deficient rats. Whereas the two studies in which increased immobility time in the FST following 2 weeks of the diet utilized the zinc-deficient diet containing 0.37 mg zinc/kg and the zinc-adequate diet containing 52.8 mg zinc/kg [21, 68], similarly, we utilized the following diets: zinc-deficient 3 mg zinc/kg; zinc-adequate 50 mg zinc/kg [66], the study which did not demonstrate a depressive-like behavior after 3 weeks of the diet utilized: zinc-deficient diet 1 mg/kg; zinc-adequate diet 30 mg/kg [25]. Hence, when interpreting data on the effectiveness of antidepressants in the zinc-deficient animals it is important to take into account the duration of the diet, the amount of the ion, and the schedule of treatment.…”

“…Fluoxetine prevented the higher levels of the hippocampal N-methyl-D-aspartate receptor (NMDAR) subunits (GluN1, GluN2A, GluN2B) and the reduced levels of phosphorylated on Serine-845 GluA1 subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) (pS485-GluA1), phosphorylated cyclic AMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) that were evoked by zinc deficiency [66]. Chronic desipramine treatment normalized the exaggerated immediate-early gene expression in the amygdala that was induced by zinc deficiency [22].…”