Little K Y, McLaughlin D P, Zhang L, McFinton P R, Dalack G W, Cook E H, Cassin B J, Watson S J
Department of Psychiatry, University of Michigan, and Ann Arbor Veterans Affairs Medical Center, 48105, USA.
Arch Gen Psychiatry. 1998 Sep;55(9):793-9. doi: 10.1001/archpsyc.55.9.793.
Results of recent radioligand binding experiments suggest that chronic cocaine exposure increases dopamine transporter (DAT) synthesis throughout the striatum of humans. However, detection of cocaine binding site increases in animals and humans has varied depending on the radioligand used. The present experiment tested the hypothesis in cocaine-using humans that synthesis of midbrain DAT messenger RNA increases parallel with increased striatal DAT binding sites.
Striatal and midbrain samples were collected during autopsy examination from human cocaine users (n = 34) and from age-, sex-, and race-matched control subjects (n = 36). Levels of DAT messenger RNA were quantified in the medial and lateral midbrain regions using in situ hybridization, and striatal DAT binding sites were assessed by quantitative autoradiography using the DAT-specific radioligand [3H]WIN 35428.
Striatal DAT binding sites were markedly increased in cocaine users, but, paradoxically, medial DAT messenger RNA levels were decreased.
Cocaine exposure has a marked effect on DAT function, but the mechanisms involved may be complex.
近期放射性配体结合实验结果表明，长期接触可卡因会增加人类整个纹状体中多巴胺转运体（DAT）的合成。然而，在动物和人类中检测到的可卡因结合位点增加情况因所使用的放射性配体而异。本实验检验了使用可卡因的人类中脑DAT信使核糖核酸（mRNA）合成与纹状体DAT结合位点增加平行这一假设。
在尸检期间从人类可卡因使用者（n = 34）以及年龄、性别和种族匹配的对照受试者（n = 36）中采集纹状体和中脑样本。使用原位杂交法定量测定中脑内侧和外侧区域的DAT信使核糖核酸水平，并使用DAT特异性放射性配体[3H]WIN 35428通过定量放射自显影法评估纹状体DAT结合位点。
可卡因使用者的纹状体DAT结合位点显著增加，但矛盾的是，中脑内侧DAT信使核糖核酸水平降低。
接触可卡因对DAT功能有显著影响，但其中涉及的机制可能很复杂。
