Involvement of glutamatergic neurotransmission in the antidepressant-like effect of zinc in the chronic unpredictable stress model of depression

Stress and excessive glutamatergic neurotransmission have been implicated in the pathophysiology of depression. Therefore, this study was aimed at investigating the influence of zinc on depressive-like behavior induced by chronic unpredictable stress (CUS), on alterations in glutamate-induced toxici...

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Bibliographic Details
Published in:Journal of Neural Transmission 2016-03, Vol.123 (3), p.339-352
Main Authors: Manosso, Luana M., Moretti, Morgana, Colla, André R., Ribeiro, Camille M., Dal-Cim, Tharine, Tasca, Carla I., Rodrigues, Ana Lúcia S.
Format: Article
Language:English
Subjects:
Animals
Antidepressive Agents - pharmacology
Behavior, Animal - drug effects
Blotting, Western
Chlorides - pharmacology
Depression
Disease Models, Animal
Female
Fluoxetine - pharmacology
Glutamine - metabolism
Hippocampus - drug effects
Hippocampus - metabolism
Medicine
Medicine & Public Health
Mice
Neurology
Neurosciences
Psychiatry
Psychiatry and Preclinical Psychiatric Studies - Original Article
Stress, Psychological - psychology
Synaptic Transmission - drug effects
Zinc Compounds - pharmacology
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Summary:Stress and excessive glutamatergic neurotransmission have been implicated in the pathophysiology of depression. Therefore, this study was aimed at investigating the influence of zinc on depressive-like behavior induced by chronic unpredictable stress (CUS), on alterations in glutamate-induced toxicity and immunocontent of proteins involved in the control of glutamatergic neurotransmission in the hippocampus of mice. Mice were subjected to CUS procedure for 14 days. From the 8th to the 14th day, mice received zinc chloride (ZnCl 2 ) (10 mg/kg) or fluoxetine (10 mg/kg, positive control) once a day by oral route. CUS caused a depressive-like behavior evidenced by the increased immobility time in the tail suspension test (TST), which was prevented by treatment with ZnCl 2 or fluoxetine. Ex vivo exposure of hippocampal slices to glutamate (10 mM) resulted in a significant decrease on cell viability; however, neither CUS procedure nor drug treatments altered this reduction. No alterations in the immunocontents of GLT-1 and GFAP or p-Akt were observed in any experimental group. The ratio of p-Akt/AKT was also not altered in any group. However, Akt immunocontent was increased in stressed mice and in animals treated with ZnCl 2 (stressed or non-stressed mice) and EAAC1 immunocontent was increased in stressed mice treated with ZnCl 2 , fluoxetine or vehicle and in non-stressed mice treated with ZnCl 2 and fluoxetine. These findings indicate a robust effect of zinc in reversing behavioral alteration induced by CUS in mice, through a possible modulation of the glutamatergic neurotransmission, extending literature data regarding the mechanisms underlying its antidepressant-like action.
ISSN:0300-9564
1435-1463
DOI:10.1007/s00702-015-1504-3