Effects of acute and chronic tianeptine administration on serotonin outflow in rats: comparison with paroxetine by using in vivo microdialysis.

Using in vivo microdialysis, we compared the effects of tianeptine (an antidepressant drug which, in marked contrast with other antidepressants, is thought to increase the uptake of serotonin (5-hydroxytryptamine, 5-HT) on extracellular 5-HT concentrations ([5-HT](ext)) in the frontal cortex and raphe nuclei of freely moving rats with those of paroxetine, a potent selective serotonin reuptake inhibitor. A single paroxetine dose (1 mg/kg, i.p.) increased [5-HT](ext) over baseline in the frontal cortex and raphe nuclei, respectively. A single administration of tianeptine (10 mg/kg, i.p.) did not change [5-HT(ext)] in the two brain regions studied. Repeated exposure to paroxetine (0.5 mg/kg) b.i.d. for 14 days induced a sixfold significant increase in basal [5-HT](ext) in the raphe nuclei. Administration of tianeptine (5 mg/kg) b.i.d. for 14 days did not affect 5-HT baseline concentrations. In rats chronically treated with either paroxetine or tianeptine, drug challenge did not alter area under the curve values. Thus, our in vivo data indicate that tianeptine and paroxetine do not exert a similar in vivo effect on the serotonergic system in rat brain.