Little K Y, Kirkman J A, Carroll F I, Clark T B, Duncan G E
Department of Psychiatry, University of North Carolina at Chapel Hill 27599-7160.
Brain Res. 1993 Nov 19;628(1-2):17-25. doi: 10.1016/0006-8993(93)90932-d.
Animal studies suggest that chronic cocaine exposure may increase the function and/or synthesis of the dopamine transporter (DAT) under certain conditions, but the literature is complex. In order to test the hypothesis that cocaine exposure alters the DAT in humans, preliminary studies were done characterizing [3H]WIN 35428 binding in human striatum from normal controls. Following these experiments, the effects of chronic cocaine were examined in post mortem striatal specimens from 7 cocaine users and 7 controls matched for age and post mortem interval, employing quantitative autoradiography. Initial saturation experiments indicated that a one-site model was preferred with a Kd of 11 +/- 4 nM. [3H]WIN 35420 binding was then examined in cocaine users and controls at 0.5, 5, 10, and 50 nM radioligand concentrations. At each concentration of [3H]WIN 35420, optical densities for cocaine-exposed subjects were increased in caudate, putamen, and accumbens. The results suggest that total numbers of binding sites were increased in cocaine users. Based on the present and previous results, it appears that the regulation of the DAT is fairly plastic, and is highly sensitive to cocaine dosing regimes and withdrawal intervals. Chronic adaptations induced by cocaine in the DAT could contribute to the symptoms of binging, withdrawal depression, and/or craving.
动物研究表明，在某些情况下，长期接触可卡因可能会增加多巴胺转运体（DAT）的功能和/或合成，但相关文献情况较为复杂。为了验证可卡因接触会改变人类DAT这一假说，开展了初步研究，对正常对照组人类纹状体中[3H]WIN 35428结合情况进行了表征。在这些实验之后，采用定量放射自显影技术，对7名可卡因使用者和7名年龄及死后间隔相匹配的对照组的死后纹状体标本中慢性可卡因的影响进行了研究。初始饱和实验表明，单一位点模型更为合适，解离常数（Kd）为11±4 nM。随后在可卡因使用者和对照组中，于0.5、5、10和50 nM的放射性配体浓度下检测[3H]WIN 35420结合情况。在每个[3H]WIN 35420浓度下，可卡因接触者在尾状核、壳核和伏隔核中的光密度均增加。结果表明，可卡因使用者的结合位点总数增加。根据目前及之前的结果，DAT的调节似乎相当具有可塑性，并且对可卡因给药方案和戒断间隔高度敏感。可卡因在DAT中诱导的慢性适应性变化可能导致暴饮暴食、戒断性抑郁和/或渴望等症状。
