Hoffman A F, Lupica C R, Gerhardt G A
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado, USA.
J Pharmacol Exp Ther. 1998 Nov;287(2):487-96.
High-speed chronoamperometric measurements were used to measure clearance of locally applied dopamine (DA) in rat brain slices containing the substantia nigra (SN) or striatum. A comparison of DA signals of similar amplitudes between brain regions revealed that DA clearance was more rapid in the striatum than in the SN, consistent with the known greater 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 selectivities 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 transporter (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 both the striatum and the SN, further confirming the functional role of the DAT in both brain regions. Local applications of d-amphetamine resulted in slow, prolonged DA-like electrochemical signals in both the SN and striatum, although the amplitude of the evoked response was larger within the striatum. In contrast, KCl-evoked depolarizations yielded rapid, detectable DA-like signals only within the striatum. Taken together, these data demonstrate the functional role of DAT in mediating DA clearance and release within both the striatum and SN.
采用高速计时电流法测量局部应用多巴胺（DA）在含有黑质（SN）或纹状体的大鼠脑片中的清除情况。对不同脑区中相似幅度的DA信号进行比较发现，纹状体中DA的清除比黑质中更快，这与已知的多巴胺转运体（DAT）在纹状体中分布更多一致。为了阐明DAT在介导黑质内DA清除中的作用，用对各种单胺转运体具有不同选择性的摄取抑制剂对脑片进行灌流。在黑质中，可卡因和诺米芬辛均显著增加了DA电化学信号的幅度和时程。然而，5-羟色胺转运体（SERT）抑制剂西酞普兰和去甲肾上腺素转运体（NET）抑制剂地昔帕明（DMI）对DA清除均未产生显著影响。此外，可卡因和诺米芬辛对纹状体和黑质中DA电化学信号清除参数的影响程度相似，进一步证实了DAT在这两个脑区中的功能作用。局部应用右旋苯丙胺在黑质和纹状体中均产生缓慢、持久的类DA电化学信号，尽管纹状体内诱发反应的幅度更大。相比之下，KCl诱发的去极化仅在纹状体内产生快速、可检测的类DA信号。综上所述，这些数据证明了DAT在介导纹状体和黑质内DA清除及释放中的功能作用。
