Jatlow P, Elsworth J D, Bradberry C W, Winger G, Taylor J R, Russell R, Roth R H
Department of Laboratory of Medicine, Yale University School of Medicine, New Haven, CT 06510.
Life Sci. 1991;48(18):1787-94. doi: 10.1016/0024-3205(91)90217-y.
High concentrations of cocaethylene (EC), the ethyl ester of benzoylecgonine, were measured in the blood of individuals who had concurrently used cocaine and ethanol. Since the powerful reinforcing effects of cocaine appear to be dependent on inhibition of dopamine reuptake in brain, we compared the effects of EC on the dopamine uptake system and its behavioral effects with those of cocaine. EC was equipotent to cocaine with respect to inhibition of binding of [3H]GBR 12935 to the dopamine reuptake complex, inhibition of [3H]dopamine uptake into synaptosomes and in its ability to increase extracellular dopamine concentration in the nucleus accumbens following its systemic administration to rats. Moreover, in rats, EC and cocaine each increased locomotor activity and rearing to the same extent following i.p. administration. In self-administration studies in primates, EC was approximately equipotent to cocaine in maintaining responding. The in vivo formation of this active, transesterified ethyl homolog of cocaine may contribute to the effects and consequences of combined cocaine and ethanol abuse.
在同时使用可卡因和乙醇的个体血液中检测到高浓度的可卡因乙烯酯（EC，即苯甲酰芽子碱的乙酯）。由于可卡因强大的强化作用似乎依赖于对大脑中多巴胺再摄取的抑制，我们将EC对多巴胺摄取系统的影响及其行为效应与可卡因的进行了比较。在抑制[3H]GBR 12935与多巴胺再摄取复合物的结合、抑制[3H]多巴胺摄取到突触体以及在对大鼠进行全身给药后增加伏隔核细胞外多巴胺浓度的能力方面，EC与可卡因相当。此外，在大鼠中，腹腔注射后，EC和可卡因各自增加运动活性和竖毛的程度相同。在灵长类动物的自我给药研究中，EC在维持反应方面与可卡因大致相当。这种活性的、经酯交换的可卡因乙基同系物在体内的形成可能有助于可卡因和乙醇联合滥用的效应和后果。
