INVOLVEMENT OF GLUTAMATERGIC NEUROTRANSMISSION IN THE ANTIDEPRESSANT-LIKE EFFECT OF ZINC IN THE CHRONIC UNPREDICTABLE STRESS MODEL OF DEPRESSION Manosso,

Introduction: Stress and excessive glutamatergic neurotransmission have been implicated in the pathophysiology of depression. Furthermore, it is well established that chronic unpredictable stress (CUS) induces depressive-like behavior and that zinc exhibits antidepressant-like effect in rodents. Objectives: The aim of this study was to investigate the influence of zinc on depressive-like behavior induced by CUS procedure and on the immunocontent of proteins involved in the control of glutamatergic neurotransmission (GLT-1, EAAC1, GFAP and Akt) in the hippocampus of mice. Materials and Methods: Female Swiss mice were submitted to CUS procedure during 14 days. From the 8th to the 14th day, mice received zinc chloride (ZnCl2) (10 mg/kg) or fluoxetine (10 mg/kg, conventional antidepressant, used as a positive control) once a day by oral route. On 15th day, behavioral parameters were analyzed. On 16th day, the biochemical analyses were performed. Results: CUS exposure caused a depressivelike behavior evidenced by the increased immobility time in the tail suspension test (TST), which was prevented by treatment with ZnCl2 or fluoxetine. No alteration in the immunocontent of GLT-1 and GFAP or Akt phosphorylation was observed in any experimental group. On the order hand, EAAC1 immunocontent was increased in stressed mice treated with ZnCl2, fluoxetine or vehicle and in non-stressed mice treated with zinc and fluoxetine. Akt immunocontent was also increased in stressed mice and in animals treated with ZnCl2 (in stressed or non-stressed mice). Conclusions: These findings indicate a robust effect of zinc in reversing behavioral alteration induced by CUS in mice, as well as change in some proteins involved in glutamatergic neurotransmission, extending literature data regarding the mechanisms underlying the antidepressant-like action of this mineral.