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 ce lls, 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 neurole ptic drugs tested, inhibited DA uptakes in DAT expressing cells, and m ost of them were shown to promote spontaneous release of DA at the sam e time. These results imply that neuroleptic drugs would cause an over flow of DA in the synaptic cleft of extrapyramidal dopaminergic neuron s, which could be one of the possible mechanisms of drug-induced tardi ve dyskinesia. (C) 1997 The Italian Pharmacological Society.