Garris P A, Wightman R M
Department of Chemistry, University of North Carolina, Chapel Hill 27599-2390, USA.
Synapse. 1995 Jul;20(3):269-79. doi: 10.1002/syn.890200311.
The pharmacological regulation of evoked extracellular dopamine was compared in the basolateral amygdaloid nucleus (BAN) and caudate-putamen (CP) of the urethane-anesthetized rat. The effects of drugs, which alter dopamine uptake, release or degradation, were examined. Dopamine efflux was elicited by electrical stimulation of ascending dopamine fibers and was monitored by fast-scan cyclic voltammetry at Nafion-coated, carbon-fiber microelectrodes. Dopamine uptake inhibitors, nomifensine (25 mg/kg) and cocaine (20 mg/kg), and the dopamine receptor antagonist, haloperidol (0.5 mg/kg), robustly increased evoked extracellular dopamine in the CP. In sharp contrast, these drugs were much less effective in the BAN. The relative potencies of the uptake inhibitors varied between the two regions. Nomifensine was more potent than cocaine in the CP, whereas cocaine was more potent that nomifensine in the BAN. The monoamine oxidase inhibitor, pargyline (75 mg/kg), and the catechol-O-methyltransferase (COMT) inhibitor, Ro 40-7592 (40 mg/kg), had small or negligible effects in either region. No electrochemical evidence was found for the formation of 3-methoxytyramine, the dopamine metabolite formed by the action of COMT on released dopamine, on the time scale of the measurements in control or after pharmacological manipulation of the degradative enzymes for dopamine. The conclusions reached are: (1) potent mechanisms for uptake and autoreceptor inhibition of release, which exist in the CP to tightly control the concentration of extracellular dopamine, are considerably weaker in the BAN; (2) the extracellular clearance of evoked dopamine in the BAN and CP is the result of cellular uptake and not degradation; and (3) these results support the view that the pharmacological regulation of extracellular dopamine is regionally distinct in the brain.
在乌拉坦麻醉的大鼠的基底外侧杏仁核（BAN）和尾状核-壳核（CP）中，对诱发的细胞外多巴胺的药理学调节进行了比较。研究了改变多巴胺摄取、释放或降解的药物的作用。通过电刺激上升的多巴胺纤维引发多巴胺外流，并在涂有Nafion的碳纤维微电极上通过快速扫描循环伏安法进行监测。多巴胺摄取抑制剂诺米芬辛（25 mg/kg）和可卡因（20 mg/kg）以及多巴胺受体拮抗剂氟哌啶醇（0.5 mg/kg）在CP中显著增加了诱发的细胞外多巴胺。与之形成鲜明对比的是，这些药物在BAN中的效果要差得多。摄取抑制剂在两个区域之间的相对效力有所不同。诺米芬辛在CP中的效力比可卡因更强，而可卡因在BAN中的效力比诺米芬辛更强。单胺氧化酶抑制剂帕吉林（75 mg/kg）和儿茶酚-O-甲基转移酶（COMT）抑制剂Ro 40-7592（40 mg/kg）在两个区域中的作用很小或可忽略不计。在对照测量期间或对多巴胺降解酶进行药理学操作后，在测量时间尺度上，未发现有电化学证据表明存在由COMT对释放的多巴胺作用形成的多巴胺代谢物3-甲氧基酪胺。得出的结论是：（1）CP中存在用于摄取和自身受体抑制释放的有效机制，以严格控制细胞外多巴胺的浓度，而在BAN中这些机制要弱得多；（2）BAN和CP中诱发多巴胺的细胞外清除是细胞摄取而非降解的结果；（3）这些结果支持了细胞外多巴胺的药理学调节在大脑中具有区域差异这一观点。
