DOPAMINE TRANSPORTER ACTIVITY IN THE SUBSTANTIA-NIGRA AND STRIATUM ASSESSED BY HIGH-SPEED CHRONOAMPEROMETRIC RECORDINGS IN BRAIN-SLICES

High-speed chronoamperometric measurements were used to measure cleara nce of locally applied dopamine (DA) in rat brain slices containing th e substantia nigra (SN) or striatum. A comparison of DA signals of sim ilar amplitudes between brain regions revealed that DA clearance was m ore rapid in the striatum than in the SN, consistent with the known gr eater distribution of the dopamine transporter (DAT) in the striatum. To clarify the role of the DAT in mediating DA clearance within the SN , slices were superfused with uptake inhibitors with different selecti vities for the various monoamine transporters. In the SN, both cocaine and nomifensine significantly increased the amplitude and time course of the DA electrochemical signal. However, neither the serotonin tran sporter (SERT) inhibitor citalopram nor the norepinephrine transporter (NET) inhibitor desipramine (DMI) produced significant effects on DA clearance. In addition, cocaine and nomifensine affected the clearance parameters of the DA electrochemical signal to a similar extent in bo th the striatum and the SN, further confirming the functional role of the DAT in both brain regions. Local applications of d-amphetamine res ulted in slow, prolonged DA-like electrochemical signals in both the S N and striatum, although the amplitude of the evoked response was larg er within the striatum. In contrast, KCI-evoked depolarizations yielde d rapid, detectable DA-like signals only within the striatum. Taken to gether, these data demonstrate the functional role of DAT in mediating DA clearance and release within both the striatum and SN.