Cocaine-sensitive, ATP-dependent dopamine uptake into striatal synaptosomes

The synaptic action of biogenic amines, in the central and peripheral nervous systems, is terminated by reuptake of the amine transmitters into the presynaptic nerve terminals (1). This neuronal uptake is temperature-dependent and exhibits saturation kinetics and stereospecificity for substrates and inhibitors (2). Striking properties of neuronal amine uptake are its complete dependency on Na + (1–3) and its sensitivity to the cardiac glycoside ouabain (3).Thus, it was hypothesized that neuronal amine uptake was a Na +-dependent active transport process like uptake of sugars and amino acids (1) and that Na +,K +-ATPase provided the energy to drive amine transport. This model prevailed for the last 20 years despite serious challenges early on (4, 5), and ATP-dependent uptake was never observed. Neuronal amine transporters are the pharmacological receptors for tricyclic antidepressants and central stimulants (e.g. cocaine). Although cocaine inhibits uptake of norepinephrine and 5-hydroxytryptamine as well as dopamine (DA), it is the last effect which correlates best with cocaine's behavioral actions (6–8). In this study, we provide evidence that the cocaine-sensitive uptake of DA into striatal synaptosomes is regulated by ATP.