Although chemically related to amineptine, the antidepressant tianeptine is not a dopamine uptake inhibitor

We investigated whether the antidepressant tianeptine shares the dopamine u ptake inhibitory properties of the chemically related antidepressant aminep tine. Tianeptine dose dependently (5, 10, 20, 40 mg/kg IP) increased locomo tor activity in mice. This stimulant effect (20 mg/kg IP) was dose dependen tly prevented not only by the D-1 dopamine receptor antagonist SCH 23390 (7 .5, 15, 30 mu g/kg SC), but also by the D-2 dopamine receptor antagonist ha loperidol (50, 100, 200 mu g/kg IP), in contrast to that elicited by dopami ne 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. T ested up to a concentration of 10-4 M, tianeptine did neither inhibit the [ H-3]dopamine uptake into mouse striatal synaptosomes nor compete in vitro w ith the specific binding of [H-3]WIN 35,428 at dopamine transporters from s triatal membranes. Finally, in mice injected IV with a tracer dose of [H-3] WIN 35,428 (1 mu Ci), the highest tested dose of tianeptine (40 mg/kg IP) d id 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. (C) 1 999 Elsevier Science Inc.