Neuroleptic drugs alter the dopamine transporter-mediated uptake and release of dopamine: A possible mechanism for drug-induced tardive dyskinesia

A bovine dopamine transporter (bDAT) cDNA was transfected into CV-1 cells, a cell line that lacks vesicular storage and release mechanisms. Using this cell line, the effects of neuroleptic drugs on DAT-mediated uptake and release of dopamine (DA) were examined. All of the neuroleptic drugs tested, inhibited DA uptakes in DAT expressing cells, and most of them were shown to promote spontaneous release of DA at the same time. These results imply that neuroleptic drugs would cause an overflow of DA in the synaptic cleft of extrapyramidal dopaminergic neurons, which could be one of the possible mechanisms of drug-induced tardive dykinesia.