Dopamine direction

Abstract

The accepted function of the dopamine transporter (DAT) is to terminate dopamine-mediated neurotransmission by removing the neurotransmitter from the synaptic cleft. In non-physiological circumstances, such as administration of amphetamine, the process can be reversed and the DAT can be made to deposit dopamine outside the neurone. Now, it seems that reversal of DAT plays a physiological role in the substantia nigra. Falkenberger et al. studied a phenomenon called dendrodendritic inhibition: dendrites influence each other's excitability by releasing dopamine in response to glutamine. They showed that this dendritic dopamine release was Ca2+ independent and could be blocked by DAT inhibitors – two findings that argue against classical vesicle-mediated exocytosis. Because excessive extracellular dopamine can be neurotoxic, the findings raise the possibility that DAT antagonists might be useful in the early stages of Parkinson's disease. [Falkenburger, B.H. et al. (2001) Science 293, 2465–2469] AB