Cocaine is thought to increase the extracellular dopamine concentration via inhibiting uptake by binding to dopamine transporters.In contrast, several studies showed that cocaine also increases extracellular dopamine by facilitating release.However, the mechanism is unclear.To address this issue, by using electrochemical amperometry for dopamine recordings, we found that dopamine overflow contained two kinetically distinct releasable vesicle pools, the fast releasable vesicle pool (RRP) and the slow releasable vesicle pool (SRP) in mouse striatum in vivo.In contrast, there is only SRP in the striatal slices.We have studied effects of cocaine on the dopamine signals in wide type vs.DAT-CI (cocaine-insensitive dopamine transporter) mice.We find that cocaine binds DAT is necessary for both classic and novel cocaine effects.