Differential sensitivity of dopamine release and clearance to 6-hydroxydopamine lesioning in rat striatum

In the present study, we compared the changes in dopamine (DA) release and clearance in the striatum after unilateral 6-hydroxydopamine (6- OHDA) lesioning of the nigrostriatal DA pathway in urethane-anesthetized rats. High-speed in vivo chronoamperometric recording techniques using Nafion-coated carbon fiber electrodes were used to evaluate extracellular DA concentration. We found that DA release, induced by local KCl application in the striatum, was maximally suppressed 21 days after lesioning. DA clearance was also affected; however, the maximal effect occurred much earlier than changes in DA release. We found that 3-7 days after lesioning, extracellular DA concentration was significantly higher in the lesioned striatum after locally applying DA. Local application of nomifensine, which blocks high affinity DA uptake, did not further potentiate the amplitude and duration of DA overflow in these animals, suggesting that the high affinity uptake of DA was abolished 3-7 days after 6-OHDA lesioning. In conclusion, our data suggest that the time courses of changes in clearance and the release of DA are differentially affected by this selective neurotoxin.