Hagelberg Nora, Aalto Sargo, Kajander Jaana, Oikonen Vesa, Hinkka Susanna, Någren Kjell, Hietala Jarmo, Scheinin Harry
Turku PET Centre, University of Turku, P.O. Box 52, FIN 20521 Turku, Finland.
Pain. 2004 May;109(1-2):86-93. doi: 10.1016/j.pain.2004.01.013.
Animal studies have shown that opioids modulate the function of dopaminergic neurons. The effect of alfentanil on cortical and thalamic binding of the D2/D3 receptor ligand [(11)C]FLB 457 was evaluated in eight healthy subjects with positron emission tomography. The simplified reference tissue model was used to calculate tracer binding potential (BP) during a baseline condition and target-controlled infusion of alfentanil, and the results were analyzed using a comparison group not receiving opioid. Behavioral and analgesic effects of alfentanil were also evaluated. In the region-of-interest analysis, alfentanil increased the BP of [(11)C]FLB 457 in the medial frontal cortex (P=0.0027), dorsolateral prefrontal cortex (P=0.027) superior temporal cortex (P=0.028), and medial thalamus (P=0.003) These results were confirmed in a voxel-based analysis, which further revealed an opioid-induced increase in [(11)C]FLB 457 BP in the anterior cingulate cortex (P<0.001). Alfentanil induced euphoria (P=0.003) and analgesia (P=0.006) Cheerfulness (r=0.918, P=0.001) and euphoria (r=0.982, P<0.001) were associated with increased BP of [(11)C]FLB 457 in the left posterior cingulate cortex, but the analgesic effect of alfentanil did not correlate with changes in [(11)C]FLB 457 BP. The results of this study demonstrate opioid-dopamine interactions in frontal and temporal cortical regions and the thalamus in healthy subjects. Increased D2/D3 tracer binding during opioid infusion may reflect decreased synaptic dopamine levels. The association of the uplifting effect of alfentanil with increased D2/D3 binding in the posterior cingulate cortex suggests that cortical dopamine may be involved in the behavioral effects of opioids.
动物研究表明，阿片类药物可调节多巴胺能神经元的功能。采用正电子发射断层扫描技术，在8名健康受试者中评估了阿芬太尼对D2/D3受体配体[(11)C]FLB 457在皮质和丘脑结合的影响。在基线状态和阿芬太尼靶控输注期间，使用简化参考组织模型计算示踪剂结合潜能（BP），并将结果与未接受阿片类药物的对照组进行分析。同时还评估了阿芬太尼的行为和镇痛效果。在感兴趣区域分析中，阿芬太尼增加了[(11)C]FLB 457在额内侧皮质（P=0.0027）、背外侧前额叶皮质（P=0.027）、颞上皮质（P=0.028）和丘脑内侧（P=0.003）的BP。这些结果在基于体素的分析中得到证实，该分析进一步显示阿片类药物可使前扣带回皮质的[(11)C]FLB 457 BP增加（P<0.001）。阿芬太尼可诱发欣快感（P=0.003）和镇痛作用（P=0.006）。愉悦感（r=0.918, P=0.001）和欣快感（r=0.982, P<0.001）与左侧后扣带回皮质[(11)C]FLB 457 BP增加相关，但阿芬太尼的镇痛效果与[(11)C]FLB 457 BP的变化无关。本研究结果表明，健康受试者额叶和颞叶皮质区域以及丘脑存在阿片类药物-多巴胺相互作用。阿片类药物输注期间D2/D3示踪剂结合增加可能反映突触多巴胺水平降低。阿芬太尼的兴奋作用与后扣带回皮质D2/D3结合增加之间的关联表明，皮质多巴胺可能参与了阿片类药物的行为效应。
