Journal of Neural Transmission

, Volume 123, Issue 3, pp 339–352 | Cite as

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

  • Luana M. Manosso
  • Morgana Moretti
  • André R. Colla
  • Camille M. Ribeiro
  • Tharine Dal-Cim
  • Carla I. Tasca
  • Ana Lúcia S. RodriguesEmail author
Psychiatry and Preclinical Psychiatric Studies - Original Article


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 (ZnCl2) (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 ZnCl2 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 ZnCl2 (stressed or non-stressed mice) and EAAC1 immunocontent was increased in stressed mice treated with ZnCl2, fluoxetine or vehicle and in non-stressed mice treated with ZnCl2 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.


Antidepressant Glutamate Stress Tail suspension test Zinc 



Brain-derived neurotrophic factor


Chronic unpredictable stress


Excitatory amino acid transporters


Glial fibrillary acidic protein


3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide




Optical density


Per os


Standard error of the mean


Tail suspension test



This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) # 308723/2013-9 and # 449436/2014-4, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), NENASC Project (PRONEX-FAPESC/CNPq) # 1262/2012-9 and CAPES/PVE 052/2012.


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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Luana M. Manosso
    • 1
  • Morgana Moretti
    • 1
    • 2
  • André R. Colla
    • 1
  • Camille M. Ribeiro
    • 1
  • Tharine Dal-Cim
    • 1
  • Carla I. Tasca
    • 1
  • Ana Lúcia S. Rodrigues
    • 1
    Email author
  1. 1.Department of Biochemistry, Center of Biological SciencesUniversidade Federal de Santa CatarinaFlorianópolisBrazil
  2. 2.Post-Graduate Nutrition Program, Center of Health SciencesUniversidade Federal de Santa CatarinaFlorianópolisBrazil

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