Liang Chih-Sung, Ho Pei-Shen, Yen Che-Hung, Yeh Yi-Wei, Kuo Shin-Chang, Huang Chang-Chih, Chen Chun-Yen, Shih Mei-Chen, Ma Kuo-Hsing, Huang San-Yuan
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taiwan.
Addict Biol. 2016 Jan;21(1):196-204. doi: 10.1111/adb.12203. Epub 2014 Dec 1.
Research on the effects of repeated opioid use on striatal dopamine transporters has yielded inconsistent results, possibly confounded by a history of methamphetamine or methadone exposure in opioid-dependent individuals. Previous studies have shown that striatal dopamine transporter density is positively correlated with the cognitive performance of healthy volunteers. This study aimed to investigate changes in striatal dopamine transporter density and their functional significance in opioid-dependent individuals. Single-photon emission computed tomography with [(99m) Tc]TRODAT-1 as a ligand was used to measure striatal dopamine transporter levels in 20 opioid-dependent individuals and 20 age- and sex-matched healthy controls. Opioid-dependent individuals had no history of methamphetamine or methadone use. The Wisconsin Card Sorting Test (WCST) was performed to assess neurocognitive function. We found that compared with healthy controls, opioid-dependent individuals showed a significant reduction in striatal dopamine transporter density. They also showed poorer performance on the WCST in terms of the trials administered, total errors, perseverative responses, perseverative errors, and non-perseverative errors. Striatal dopamine transporter levels negatively correlated with non-perseverative errors not only in opioid-dependent individuals but also in healthy controls. These findings suggest that in human, repeated opioid exposure reduces striatal dopamine transporter density, which can be associated with non-perseverative errors. Non-perseverative errors may be one of the more sensitive parameters in WCST to identify working memory deficits associated with striatal dopamine transporter reduction. Moreover, we suggest that whether opioid-associated neurotoxicity is reversible depends on the brain region.
关于反复使用阿片类药物对纹状体多巴胺转运体影响的研究结果并不一致,这可能是由于阿片类药物依赖个体有甲基苯丙胺或美沙酮接触史而造成混淆。先前的研究表明,纹状体多巴胺转运体密度与健康志愿者的认知表现呈正相关。本研究旨在调查阿片类药物依赖个体纹状体多巴胺转运体密度的变化及其功能意义。以[(99m)Tc]TRODAT-1为配体的单光子发射计算机断层扫描用于测量20名阿片类药物依赖个体和20名年龄及性别匹配的健康对照者的纹状体多巴胺转运体水平。阿片类药物依赖个体无甲基苯丙胺或美沙酮使用史。采用威斯康星卡片分类测验(WCST)评估神经认知功能。我们发现,与健康对照者相比,阿片类药物依赖个体的纹状体多巴胺转运体密度显著降低。他们在WCST中的表现也较差,在试验次数、总错误数、持续性反应、持续性错误和非持续性错误方面均如此。纹状体多巴胺转运体水平不仅在阿片类药物依赖个体中,而且在健康对照者中均与非持续性错误呈负相关。这些发现表明,在人类中,反复接触阿片类药物会降低纹状体多巴胺转运体密度,这可能与非持续性错误有关。非持续性错误可能是WCST中用于识别与纹状体多巴胺转运体减少相关的工作记忆缺陷的更敏感参数之一。此外,我们认为阿片类药物相关的神经毒性是否可逆取决于脑区。