Tianeptine reverses stress-induced asymmetrical hippocampal volume and N-acetylaspartate loss in rats: An in vivo study

Stress-induced hippocampal volume loss and decrease in N-acetylaspartate (NAA) level have been reported to be associated with impaired neural plasticity and neuronal damage in adults. Accordingly, reversing structural and metabolite damage in the hippocampus may be a desirable goal for antidepressant therapy. The present study investigated the effects of tianeptine on chronic stress-induced hippocampal volume loss and metabolite alterations in vivo in 24 Sprague-Dawley rats. Rats were subjected to a consecutive 28-day forced swimming test stress. Tianeptine (50 mg/kg) or saline was administered intragastrically 4 h after swimming each day. Spontaneous behaviors, serum corticosterone concentration, hippocampal volume and NAA level were evaluated after stress. Chronic tianeptine treatment counteracted the chronic stress-induced suppression of spontaneous behaviors, elevated serum corticosterone concentration, reduced hippocampal volume and decreased NAA level. Moreover, we found asymmetrical right–left hippocampal volume loss in stressed rats, with the left hippocampus more sensitive to chronic stress than the right hippocampus. In addition, stressed rats showed a decreased level of hippocampal metabolites, without significant loss of hippocampal volume. These findings provide experimental evidence for impaired structural plasticity of the brain being an important feature of depressive illness and suggest that prophylactic tianeptine treatments could reverse structural changes in brain. The structural and neurochemical alterations in the hippocampus may be valuable indexes for evaluating the prophylactic and curative effect of antidepressant treatments in depressive and stress-related disorders.