In vitro studies were performed on glutamatergic thalamocortical neurons cultured from rat embryos removed on embryonic day 18 (E18). Cells were observed for up to 33 days after initial culturing. The investigation concerned the effects of drugs that act on the serotonin transporter on the appearance of 5HT (assessed via staining) in thalamocortical regions. It is assumed that glutamatergic cells "borrow" 5HT that is transported from raphe cells during development. The addition of serotonin to cell cultures increased serotonin transporter (SERT) activity overall and shifted the peak for SERT expression and loss of SERT to a later age than untreated cultures. Like additional 5HT, adding MDMA to the cells produced an increase in peak SERT expression and a rightward shift in SERT expression and loss. In contrast, when either cocaine or fluoextine were added along with 5HT, they eliminated the peak in SERT expression and prevented additional 5HT from producing a shift in time-course for SERT expression and loss of SERT in cultures. The addition of MDMA altered the amount of functional SERT in cell cultures. Overall, these findings suggest that MDMA, cocaine and fluoxetine could alter the development of glutamatergic neurons in the thalamocortical area by altering the concentration of 5HT and SERT, and by shifting peak concentration to a later point in time, and by potentially altering course of brain development. Given that both MDMA and cocaine can act as serotonin uptake inhibitors, and given that both possess dopaminergic activity, it would seem that serotonin release versus reuptake, and perhaps differences in noradrenergic activity, might also be involved in the differential activity of these two drugs in this study.