EFFECTS OF COCAINE ON SODIUM-DEPENDENT DOPAMINE UPTAKE IN RAT STRIATAL SYNAPTOSOMES

Initial velocity of uptake of dopamine (DA) has been measured in the p resence of 1muM cocaine as a function of both [DA] and [Na]. Although DA uptake is overwhelmingly dependent on sodium, it appears that a sma ll amount of DA uptake takes place in the absence of sodium. This cont rasts with a previous study of the sodium dependence of uptake without cocaine (referred to below as control), in which uptake was found to be 100% sodium dependent. The data were fitted to several rapid equili brium models and the minimal best fit model identified. The interactio n of transporter (C), DA (S), and Na+ (Na) in this present model is id entical to the reaction scheme found previously to fit control data (n o cocaine). Whereas the control model required translocation only as C Na2S, in the presence of cocaine (I), two additional translocated spec ies are required to fit the data (CS and CNaS). Another previous study of the interaction of carrier and cocaine at a constant [Na]0 predict ed that cocaine interacts with a transporter site other than the DA bi nding site and that uptake takes place as CS and CSI. The present resu lts are consistent with the assumption that the CS and CNaS forms of t he present model are actually CSI and CNaSI, since they are required t o fit a model of the sodium dependence in the presence of cocaine, but are not required in the absence of cocaine.