Striatal dopaminergic abnormalities in human cocaine users.
Striatal dopaminergic abnormalities in human cocaine users.
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DOI：
10.1176/ajp.156.2.238
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发表时间：
1999-02
期刊：
影响因子：
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通讯作者：
K. Y. Little;L. Zhang;T. Desmond;K. Frey;G. Dalack;B. Cassin
中科院分区：
文献类型：
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作者：
K. Y. Little;L. Zhang;T. Desmond;K. Frey;G. Dalack;B. Cassin
研究目的：以往的人体死后实验表明，慢性可卡因使用者纹状体内多巴胺摄取部位异常增多，这可能与可卡因戒断症状如抑郁和自杀有关。以前的不一致的结果可能与选择性放射性配体亲和力的变化或共存的多巴胺神经元的损失。方法在本研究中，结合的可卡因类似物[3 H]WIN 35428多巴胺转运蛋白进行了测定，在死后纹状体样品从15个可卡因使用的主题和15个匹配的比较主题，以确定是否有差异的结合位点的数量或亲和力。结合囊泡单胺转运蛋白，总多巴胺能末梢的措施，也进行了评估，通过使用放射性配体（+）-[3 H]二氢丁苯那嗪（DTBZ）。结果可卡因使用者纹状体[3 H]WIN 35428结合位点明显增多：可卡因使用者的平均Bmax值为9.0 fmol结合/μ g蛋白（SD = 2.8），而对照组仅为6.0（SD = 1.7）。慢性可卡因使用的严重程度与[3 H]WIN 35428结合水平显著相关。可卡因使用者的[3 H]DTBZ结合率（平均值= 330 nCi/mg，SD = 42）显著低于对照受试者（平均值= 374，SD = 68）。结论：本研究结果证实可卡因使用者在多巴胺能神经元上有大量的多巴胺转运体结合位点，尽管总多巴胺终末的数量明显较少。这些异常可能导致慢性可卡因滥用者的主观体验和行为特征的异常。
OBJECTIVE Previous human postmortem experiments have shown an abnormally high number of dopamine uptake sites in the striatum of chronic cocaine users, which might contribute to cocaine withdrawal symptoms such as depression and suicidality. Previous inconsistencies in results were perhaps related to selective radioligand affinity changes or a coexisting loss of dopamine neurons. METHOD In the present study, binding of the cocaine analog [3H]WIN 35428 to the dopamine transporter was assayed in postmortem striatal samples from 15 cocaine-using subjects and 15 matched comparison subjects to determine whether there were differences in number of binding sites or in affinity. Binding to the vesicular monoamine transporter, a measure of total dopaminergic terminals, was also assessed by using the radioligand (+)-[3H]dihydrotetrabenazine (DTBZ). RESULTS Striatal [3H]WIN 35428 binding sites were significantly more numerous in the cocaine users: the mean Bmax value was 9.0 fmol bound/microg protein (SD = 2.8) for the cocaine users but only 6.0 (SD = 1.7) for the comparison subjects. Severity of chronic cocaine use was significantly related to [3H]WIN 35428 binding level. [3H]DTBZ binding was significantly lower in the cocaine users (mean = 330 nCi/mg, SD = 42) than in the comparison subjects (mean = 374, SD = 68). CONCLUSIONS The present results confirm that cocaine users have a high number of dopamine transporter binding sites on dopaminergic neurons, despite an apparent low number of total dopamine terminals. These abnormalities may contribute to the abnormalities in subjective experience and behavior characteristic of chronic cocaine abusers.