INFLUENCE OF THE NOVEL ANTIDEPRESSANT TIANEPTINE ON NEUROCHEMICAL, NEUROENDOCRINOLOGICAL, AND BEHAVIORAL-EFFECTS OF STRESS IN RATS

Tianeptine is a novel tricyclic agent that activates the neuronal uptake of serotonin (5-hydroxytryptamine, 5-HT). Taking into account the antidepressant effect of tianeptine in animals and humans, we have measured the influence of a pretreatment with tianeptine (10 mg/kg IP 1 hr beforehand) on some consequences of a single 2-hr restraint stress session in male rats. Thus, we have analyzed (1) 5-HT metabolism in various brain regions and plasma glucose (an index of sympathoadrenal activity) and corticosterone levels at the end of stress, and (2) open field scores 18-19 hr after immobilization in saline- or tianeptine-pretreated rats. Tianeptine was found to leave unaltered stress-induced increases in cortical, hippocampal, hypothalamic, midbrain, and striatal serotonergic metabolism. Similarly, stress-elicited elevations in plasma glucose and corticosterone levels were not affected by tianeptine pretreatment. On the other hand, tianeptine pretreatment reversed stress-induced deficit in exploratory activity. To test whether the latter positive effect of tianeptine was associated with changes in plasma glucose and corticosterone levels during the early phase of stress, we have measured plasma glucose and corticosterone levels (at 0, 5, 15, 30, and 60 min) in resting and stressed (catheterized) rats. The results indicated that tianeptine pretreatment did not alter plasma glucose and corticosterone early responses to stress. Although this study confirmed the antidepressant effect of tianeptine, the neurochemical and neuroendocrinological mechanisms underlying this positive effect remain to be determined.