Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine

Stress-induced structural remodeling in the adult hippocampus, involving de branching and shortening of dendrites and suppression of neurogenesis, prov ides a cellular basis for understanding the impairment of neural plasticity in the human hippocampus in depressive illness. Accordingly, reversal of s tructural remodeling may be a desirable goal for antidepressant therapy. Th e present study investigated the effect of tianeptine, a modified tricyclic antidepressant, in the chronic psychosocial stress model of adult male tre e shrews (Tupaia belangeri), a model with high validity for research on the pathophysiology of major depression. Animals were subjected to a 7-day per iod of psychosocial stress to elicit stress-induced endocrine and central n ervous alterations before the onset of daily oral administration of tianept ine (50 mg/kg). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy, cell proliferation in the dentat e gyrus was quantified by using BrdUrd immunohistochemistry, and hippocampa l volume was measured post mortem. Chronic psychosocial stress significantl y decreased in vivo concentrations of N-acetyl-aspartate (-13%), creatine a nd phosphocreatine (-15%), and choline-containing compounds (-13%). The pro liferation rate of the granule precursor cells in the dentate gyrus was red uced (-33%). These stress effects were prevented by the simultaneous admini stration of tianeptine yielding normal values. in stressed animals treated with tianeptine, hippocampal volume increased above the small decrease prod uced by stress alone. These findings provide a cellular and neurochemical b asis for evaluating antidepressant treatments with regard to possible rever sal of structural changes in brain that have been reported in depressive di sorders.