Fehr Christoph, Yakushev Igor, Hohmann Nina, Buchholz Hans-Georg, Landvogt Christian, Deckers Hanna, Eberhardt Alexandra, Kläger Marie, Smolka Michael N, Scheurich Armin, Dielentheis Thomas, Schmidt Lutz G, Rösch Frank, Bartenstein Peter, Gründer Gerhard, Schreckenberger Mathias
Department of Psychiatry, University of Mainz, Untere Zahlbacher Strasse 8, 55131 Mainz, Germany.
Am J Psychiatry. 2008 Apr;165(4):507-14. doi: 10.1176/appi.ajp.2007.07020352. Epub 2008 Mar 3.
All drugs of abuse induce a phasic dopamine release within the striatum that does not undergo habituation. Prolonged substance consumption impairs the natural function of the mesolimbic dopamine system, as shown by a decrease in the availability of striatal dopamine 2 (D(2)) receptors in patients suffering from cocaine, heroin, amphetamine, and alcohol dependence. However, it is unclear whether similar changes can also be observed in heavy-smoking nicotine-dependent smokers.
In vivo D(2)/D(3) receptor availability was determined with [ (18)F]fallypride positron emission tomography in 17 heavy-smoking nicotine-dependent subjects and in 21 age-matched never-smoking comparison subjects. The smokers were scanned twice: first, during a period of usual consumption and second, 24 hours after smoking cessation.
Independent of the withdrawal status, the nicotine-dependent smokers displayed significantly less availability of D(2)/D(3) receptors within the bilateral putamen functionally covering parts of the dorsal striatum, as compared to the never-smoking subjects. Nicotine craving under the consumption condition correlated positively with D(2)/D(3) receptor availability within the ventral striatum but negatively with D(2)/D(3) receptor availability within the anterior cingulate and inferior temporal cortex.
Similar to other types of substance abuse, nicotine dependence is associated with low availability of dorsal striatal D(2)/D(3) receptors. In contrast to previous findings on abstinent alcohol-dependent patients, nicotine craving seems to be maintained by a region-specific shift in D(2)/D(3) receptor availabilities, with higher availability within the ventral striatum but lower availability within the anterior cingulate and inferior temporal cortex.
所有滥用药物都会在纹状体内诱发阶段性多巴胺释放，且这种释放不会产生习惯化。长期使用药物会损害中脑边缘多巴胺系统的自然功能，这在可卡因、海洛因、苯丙胺和酒精依赖患者中表现为纹状体多巴胺2（D(2)）受体的可用性降低。然而，目前尚不清楚在重度吸烟的尼古丁依赖吸烟者中是否也能观察到类似变化。
利用[ (18)F]氟哌利多正电子发射断层扫描技术，对17名重度吸烟的尼古丁依赖者和21名年龄匹配的从不吸烟者进行体内D(2)/D(3)受体可用性测定。吸烟者接受两次扫描：第一次在正常吸烟期间，第二次在戒烟24小时后。
与从不吸烟者相比，无论是否处于戒断状态，尼古丁依赖吸烟者双侧壳核（其功能覆盖部分背侧纹状体）内D(2)/D(3)受体的可用性均显著降低。吸烟状态下的尼古丁渴望与腹侧纹状体内D(2)/D(3)受体可用性呈正相关，但与前扣带回和颞下回皮质内D(2)/D(3)受体可用性呈负相关。
与其他类型的药物滥用相似，尼古丁依赖与背侧纹状体D(2)/D(3)受体可用性低有关。与先前对戒酒的酒精依赖患者的研究结果不同，尼古丁渴望似乎是由D(2)/D(3)受体可用性的区域特异性变化维持的，腹侧纹状体内可用性较高，而前扣带回和颞下回皮质内可用性较低。
