IN-VIVO ELECTROCHEMICAL STUDIES OF DOPAMINE CLEARANCE IN THE RAT SUBSTANTIA-NIGRA - EFFECTS OF LOCALLY APPLIED UPTAKE INHIBITORS AND UNILATERAL 6-HYDROXYDOPAMINE LESIONS

High-speed chronoamperometric recordings were used to measure the upta ke and clearance of locally applied dopamine (DA) within the substanti a nigra (SN) of anesthetized rats. To establish that DA clearance with in the SN was mediated primarily by the DA transporter (DAT) rather th an the norepinephrine transporter (NET) or the serotonin transporter ( SERT), we locally applied uptake inhibitors with different selectivity profiles for the various amine transporters. Nomifensine, a DAT/NET i nhibitor, significantly potentiated both the amplitude and the time co urse of the DA signals. In contrast, neither the selective NET inhibit or desipramine, nor the selective SERT inhibitor citalopram affected t he DA signal, suggesting that NET and SERT do not contribute to DA upt ake and clearance within the regions of the SN studied over the concen tration ranges (1-5 mu M) used. In unilaterally 6-hydroxydopamine-lesi oned rats, the time course of the DA signal was increased in both the lesioned SN and striatum, relative to the unlesioned hemisphere, indic ating toss of DAT and decreased DA uptake and clearance. In addition, when identical amounts of DA were injected in the striatum and SN, pea k signal amplitudes were larger in the SN, suggesting that the amplitu des are related to the number of DAT sites in a given region of brain tissue. For signals of equivalent amplitudes, clearance rates were low er in the SN than in the striatum, consistent with a lower capacity fo r DAT-mediated DA uptake within the SN. These results suggest that the DAT is the major transporter responsible for DA clearance within the rat SN.