Di Ciano P., Coury A., Depoortere R.Y., Egilmez Y., Lane J.D., Emmett-Oglesby M.W., Lepiane F.G., Phillips A.G., Blaha C.D.
Department of Psychology, University of British Columbia, Vancouver, B.C., Canada V6T 1Z4.
Behav Pharmacol. 1995 Jun;6(4):311-322.
Changes in extracellular concentrations of dopamine (DA) were measured in vivo in the nucleus accumbens of the rat during intravenous self-administration of either cocaine (0.25, 0.5, 1.0mg/infusion) or d-amphetamine (0.05, 0.1, 0.2mg/infusion). Drug intake was limited to 12 self-administered infusions per session for each drug/dose combination. Changes in extra-cellular DA concentrations were measured by two different techniques: chronoamperometry in conjunction with chronically-implanted stearate-modified carbon paste electrodes, or intracerebral microdialysis with off-line analyses using high performance liquid chromatography with electrochemical detection (HPLC-ED). Significant increases in extracellular DA concentrations were observed with both in vivo techniques during self-administration of each dose of cocaine or d-amphetamine. For each drug, the magnitude of change during the first hour of the test session was comparable across doses. However, the change observed over the first 2h period, as measured by microdialysis and HPLC-ED, revealed a dose effect for cocaine, but no dose-response effect for d-amphetamine. The duration of the drug-induced elevation was increased significantly as a function of dose with both cocaine and d-amphetamine. Data from the microdialysis experiments indicated that the high dose of d-amphetamine (0.2mg/infusion) produced a significantly greater increase in extracellular DA concentrations in the nucleus accumbens than did the high dose of cocaine (1.0mg/infusion), but that comparable changes were induced by doses of 0.1mg/infusion of d-amphetamine and 1.0mg/infusion of cocaine, respectively. Each dose of both psychostimulant drugs also produced a significant decrease in dihydroxyphenylacetic acid (DOPAC) levels. The latter finding indicated that the electrochemical signal measured in these studies was not due to the oxidation of DOPAC. These results confirm that self-administration of cocaine or d-amphetamine by the rat is accompanied by a significant increase in extracellular DA concentrations in the nucleus accumbens. The fact that two different psychomotor stimulant drugs of abuse have qualitatively similar neurochemical correlates when self-administered, adds credence to the hypothesis that their reinforcing properties are related to dynamic changes in DA concentrations in the ventral striatal region of the brain.
在大鼠伏隔核中，于体内测量静脉注射可卡因（0.25、0.5、1.0毫克/注射）或右旋苯丙胺（0.05、0.1、0.2毫克/注射）进行自我给药期间细胞外多巴胺（DA）浓度的变化。每种药物/剂量组合的药物摄入量限制为每次实验12次自我给药注射。细胞外DA浓度的变化通过两种不同技术测量：结合长期植入的硬脂酸修饰碳糊电极的计时电流分析法，或使用高效液相色谱电化学检测（HPLC - ED）进行离线分析的脑内微透析法。在每次注射可卡因或右旋苯丙胺的自我给药期间，两种体内技术均观察到细胞外DA浓度显著增加。对于每种药物，测试时段第一小时内的变化幅度在各剂量间具有可比性。然而，通过微透析和HPLC - ED测量，在最初2小时内观察到的变化显示可卡因存在剂量效应，而右旋苯丙胺不存在剂量 - 反应效应。药物诱导升高的持续时间随可卡因和右旋苯丙胺的剂量显著增加。微透析实验数据表明，高剂量的右旋苯丙胺（0.2毫克/注射）比高剂量的可卡因（1.0毫克/注射）在伏隔核中产生的细胞外DA浓度增加显著更大，但分别由0.1毫克/注射的右旋苯丙胺和1.0毫克/注射的可卡因诱导出相当的变化。两种精神兴奋剂药物的每种剂量也使二羟基苯乙酸（DOPAC）水平显著降低。后一发现表明这些研究中测量的电化学信号并非由于DOPAC的氧化。这些结果证实大鼠自我给药可卡因或右旋苯丙胺会伴随着伏隔核中细胞外DA浓度的显著增加。当自我给药时，两种不同的滥用精神运动兴奋剂药物具有定性相似的神经化学关联这一事实，为它们的强化特性与脑腹侧纹状体区域DA浓度的动态变化相关这一假设增添了可信度。
