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 tan anti depressant drug which, in marked contrast with other antidepressants, is th ought to increase the uptake of serotonin (5-hydroxytryptamine, 5-HT) on ex tracellular 5-HT concentrations ([5-HT](ext)) in the frontal cortex and rap he nuclei of freely moving rats with those of paroxetine, a potent selectiv e serotonin reuptake inhibitor. A single paroxetine dose (1 mg/kg, i.p.) in creased [5-HT](ext) over baseline in the frontal cortex and raphe nuclei, r espectively. A single administration of tianeptine (10 mg/kg, i.p.) did not change [5-HText] in the two brain regions studied. Repeated exposure to pa roxetine (0.5 mg/kg) b.i.d. for 14 days induced a sixfold significant incre ase 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. I n rats chronically treated with either paroxetine or tianeptine, drug chall enge did not alter area under the curve values. Thus, our in vivo data indi cate that tianeptine and paroxetine do not exert a similar in vivo effect o n the serotonergic system in rat brain. (C) 2000 Elsevier Science B.V. All rights reserved.