Scarponi M, Bernardi G, Mercuri N B
IRCCS S. Lucia, Rome, Italy.
Eur J Neurosci. 1999 Feb;11(2):593-8. doi: 10.1046/j.1460-9568.1999.00482.x.
To determine the functional interactions occurring between amphetamine and cocaine-like drugs on a single neuron, we used intracellular single-electrode voltage-clamp recordings from dopaminergic cells of the rat midbrain maintained in vitro. In the presence of cocaine (3-30 microM), the outward current caused by amphetamine (100 microM) on cells held at about -60 mV was attenuated. The degree of attenuation of the amphetamine-induced response was almost the same for 3 and 30 microM cocaine (44 and 51% of control, respectively). This effect of cocaine was reversible. We also tested other DA-uptake inhibitors (nomifensine and 4-phenyltetrahydroisoquinoline) against the amphetamine-induced outward current. Both drugs enhanced the effects of dopamine (DA) while reducing the outward response caused by amphetamine. Pretreatment of the animals with reserpine (12 mg/kg/i.p.), which irreversibly depletes the vesicular DA stores, neither affected the amplitude of the current caused by amphetamine nor changed the cocaine-induced attenuation of the membrane responses to amphetamine. Interestingly, when amphetamine (3 microM) was superfused on the dopaminergic neurons prior and during the application of cocaine, the DA-uptake blocker was no longer able to potentiate the outward response caused by the superfusion of DA. Taken together, these data suggest that: (i) amphetamine and cocaine interact with the DA transporter to produce distinct actions which under certain circumstances can compete with each other; (ii) the amphetamine-induced release of DA from the somata and dendrites of the dopaminergic cells is, at least in part, related to the reverse operation of the DA transporter and is not dependent on the integrity of the vesicular content of the catecholamine.
为了确定苯丙胺与可卡因类药物在单个神经元上发生的功能相互作用，我们使用细胞内单电极电压钳记录法，对体外培养的大鼠中脑多巴胺能细胞进行记录。在存在可卡因（3 - 30微摩尔）的情况下，苯丙胺（100微摩尔）在约 -60毫伏的膜电位下引起的外向电流在细胞上被减弱。对于3微摩尔和30微摩尔的可卡因，苯丙胺诱导反应的减弱程度几乎相同（分别为对照的44%和51%）。可卡因的这种作用是可逆的。我们还测试了其他多巴胺摄取抑制剂（诺米芬辛和4 - 苯基四氢异喹啉）对苯丙胺诱导的外向电流的影响。两种药物都增强了多巴胺（DA）的作用，同时减少了苯丙胺引起的外向反应。用利血平（12毫克/千克/腹腔注射）对动物进行预处理，利血平不可逆地耗尽囊泡中的多巴胺储存，既不影响苯丙胺引起的电流幅度，也不改变可卡因诱导的对苯丙胺膜反应的减弱。有趣的是，当在应用可卡因之前和期间将苯丙胺（3微摩尔）灌流到多巴胺能神经元上时，多巴胺摄取阻滞剂不再能够增强由多巴胺灌流引起的外向反应。综上所述，这些数据表明：（i）苯丙胺和可卡因与多巴胺转运体相互作用产生不同的作用，在某些情况下它们可以相互竞争；（ii）多巴胺能细胞的胞体和树突中由苯丙胺诱导的多巴胺释放，至少部分与多巴胺转运体的反向运作有关，并且不依赖于儿茶酚胺囊泡内容物的完整性。
