We investigated whether the antidepressant tianeptine shares the dopamine uptake inhibitory properties of the chemically related antidepressant amineptine. Tianeptine dose dependently (5, 10, 20, 40 mg/kg IP) increased locomotor activity in mice. This stimulant effect (20 mg/kg IP) was dose dependently prevented not only by the D1 dopamine receptor antagonist SCH 23390 (7.5. 15, 30 microg/kg SC), but also by the D2 dopamine receptor antagonist haloperidol (50, 100, 200 microg/kg IP), in contrast to that elicited by dopamine uptake inhibitors. Where the latter prevent dexamphetamine-induced (3 mg/kg SC) reversion of akinesia in mice pretreated with reserpine (4 mg/kg SC, 5 h before test), tianeptine (20 mg/kg IP, 30 min before test) did not. Tested up to a concentration of 10-4 M, tianeptine did neither inhibit the [3H]dopamine uptake into mouse striatal synaptosomes nor compete in vitro with the specific binding of [3H]WIN 35,428 at dopamine transporters from striatal membranes. Finally, in mice injected IV with a tracer dose of [3H]WIN 35,428 (1 microCi), the highest tested dose of tianeptine (40 mg/kg IP) did not reduce the specific binding of the radioligand to striatal dopamine transporters. It is concluded that the antidepressant effect of tianeptine does not depend upon a blockade of the neuronal dopamine transporter.