(A) Application of bk-MDDMA (20 μM) during constant perfusion of DA counteracts the inward DA-induced current. After removal of bk-MDDMA, a DA-induced inward current is observed; however, after DA is washed out, the current goes above baseline (above dashed line). A second exposure to bk-MDDMA induces a small outward current that returns to the level the baseline was shifted to. A subsequent DA-induced hDAT current is similar to the initial DA response, and after the last DA application is washed out, the baseline remains shifted. (B) At hSERT, bk-MDDMA (20 μM) induces a small block of the endogenous leak current, but in contrast to what happens at hDAT, after washing out bk-MDDMA the holding current at hSERT returns to its original level. (C) Application of ABDP shifts the baseline even in the presence of DA. ABDP application (20 μM) is applied to hDAT in the presence of DA, which elicits a counteracting hDAT-mediated current. After removal of ABDP application, the DA present induces an hDAT-mediated inward current; however, after DA is washed out, the current goes above baseline. A second exposure to ABDP application induces a small outward current. A subsequent DA-induced hDAT current is similar to the initial DA response, and after the last DA application is washed out, the baseline remains shifted. (D) ABDP (20 μM) induces an hSERT-mediated inward current that does not return to baseline. Note: All DA and 5HT challenges are 5 μM.