Decreased prefrontal cortical dopamine transmission in alcoholism.
Decreased prefrontal cortical dopamine transmission in alcoholism.
复制标题
DOI：
10.1176/appi.ajp.2014.13121581
复制
发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Frankle WG
中科院分区：
文献类型：
--
作者：
Narendran R;Mason NS;Paris J;Himes ML;Douaihy AB;Frankle WG
基础研究表明，前额叶皮质多巴胺的最佳水平对各种执行功能至关重要，如工作记忆，注意力，抑制控制和风险/奖励决策-所有这些都在酒精中毒等成瘾性疾病中受损。基于这一点，以及对酗酒者的成像研究表明纹状体中的多巴胺减少，我们假设酗酒者的前额叶皮层多巴胺传递减少。为了验证这一假设，我们使用安非他明和[11 C]FLB 457正电子发射断层扫描（PET）来测量一组21名最近戒酒的酗酒者和匹配的健康对照组的皮质多巴胺传输。[11 C]FLB 457结合电位（BPND）在0.5 mg kg−1 d-苯丙胺之前和之后，使用动脉输入函数进行动力学分析。与健康对照组相比，酗酒者皮质区域中安非他明诱导的[11 C]FLB 457结合电位（Δ BPND）位移显著较小。在酗酒者中表现出较低多巴胺传递的皮质区域包括背外侧前额叶皮质、内侧前额叶皮质、眶额叶皮质、颞叶皮质和内侧颞叶。这项研究的结果第一次明确地证明了酗酒者大脑皮层多巴胺传递的减少。进一步的研究是必要的，以了解皮质多巴胺减少的临床相关性，是否与执行功能受损，复发和酗酒的结果。
Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such working memory, attention, inhibitory control and risk/reward decisions--all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies in alcoholics that have demonstrated less dopamine in the striatum, we hypothesized decreased dopamine transmission in the prefrontal cortex in alcoholism. To test this hypothesis, we used amphetamine and [11C]FLB 457 positron emission tomography (PET) to measure cortical dopamine transmission in a group of 21 recently abstinent alcoholics and matched healthy controls. [11C]FLB 457 binding potential (BPND) was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg−1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (Δ BPND) was significantly smaller in the cortical regions in alcoholics compared to healthy controls. Cortical regions that demonstrated lower dopamine transmission in alcoholics included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex and medial temporal lobe. The results of this study for the first time unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.