Tupala E, Kuikka J T, Hall H, Bergström K, Särkioja T, Räsänen P, Mantere T, Hiltunen J, Vepsäläinen J, Tiihonen J
Department of Forensic Psychiatry, Niuvanniemi Hospital, Finland.
Neuroimage. 2001 Jul;14(1 Pt 1):87-94. doi: 10.1006/nimg.2001.0793.
Dopaminergic mechanisms are involved in the positive reinforcing and addicting effects of alcohol. Positron emission tomography (PET) and single photon emission tomography (SPET) studies have indicated alterations in striatal dopamine transporters (DAT) and in presynaptic dopamine (DA) function in alcoholics, although also contradictory results have been reported. Normal variations in blood flow, metabolism, and receptor densities are apparently important to brain function. Such variations are known to decrease during pathophysiological processes, such as epilepsy, whereas normal receptor distributions are broadly heterogenous. We evaluated the densities and heterogeneities of striatal DAT in 8 adult-onset, Cloninger type I alcoholics and 10 controls using [125I]N-(3-iodoprop-2E-enyl)-2beta-carbomethoxy-3beta- (4'-methylphenyl)nortropane ([125I]PE2I) as a ligand for human postmortem whole hemisphere autoradiography, which provided high resolution images of the brain when compared with in vivo PET and SPET. The mean density and heterogeneity of DAT were markedly lower in the alcoholics. A significant linear correlation existed between DAT density and heterogeneity, as well as between DAT densities in the nucleus accumbens and in the dorsal striatum (caudate and putamen) in alcoholics, but not consistently in controls. The observed low DAT density and heterogeneity in the dorsal striatum suggest that type 1 alcoholics may have a dysfunctional DA system. These data indicate that human whole hemisphere autoradiography with the analysis of binding heterogeneity may be a relevant tool to measure pathological processes in the brain.
多巴胺能机制与酒精的正性强化和成瘾作用有关。正电子发射断层扫描（PET）和单光子发射断层扫描（SPET）研究表明，酗酒者纹状体多巴胺转运体（DAT）和突触前多巴胺（DA）功能存在改变，不过也有相互矛盾的结果报道。血流、代谢和受体密度的正常变化显然对脑功能很重要。已知这种变化在病理生理过程（如癫痫）中会降低，而正常的受体分布广泛存在异质性。我们使用[125I]N-（3-碘丙-2E-烯基）-2β-甲氧羰基-3β-（4'-甲基苯基）去甲托烷（[125I]PE2I）作为配体，对8名成年起病的克隆宁格I型酗酒者和10名对照者进行了纹状体DAT密度和异质性评估，用于人类死后全脑半球放射自显影，与活体PET和SPET相比，该方法能提供高分辨率的脑图像。酗酒者DAT的平均密度和异质性明显较低。酗酒者中，DAT密度与异质性之间、伏隔核和背侧纹状体（尾状核和壳核）的DAT密度之间存在显著的线性相关性，但在对照者中并非始终如此。在背侧纹状体中观察到的低DAT密度和异质性表明，I型酗酒者可能存在DA系统功能障碍。这些数据表明，结合异质性分析的人类全脑半球放射自显影可能是测量脑内病理过程的一种相关工具。
