Thiruchselvam Thulasi, Wilson Alan A, Boileau Isabelle, Le Foll Bernard
Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Alcohol Clin Exp Res. 2017 Jun;41(6):1112-1119. doi: 10.1111/acer.13403. Epub 2017 May 29.
Previous positron emission tomography (PET) studies exploring the effect of acute alcohol on dopamine (DA) levels have yielded inconsistent results, with only some studies suggesting increased synaptic DA levels after an alcohol challenge. The D /D agonist radiotracer, [ C]-(+)-propyl-hexahydro-naphtho-oxazin ([ C]-(+)-PHNO), has greater sensitivity to synaptic DA fluctuation than previously used antagonist radiotracers and is in principle more suitable for imaging alcohol-induced changes in DA. Its high affinity for the D receptor also enables measuring changes in D -rich brain areas which have previously been unexplored. The aim of this study was to investigate whether alcohol reduces [ C]-(+)-PHNO binding in the striatum and in D -rich extra-striatal areas.
Eight healthy drinkers underwent 2 [ C]-(+)-PHNO PET scans following alcohol and placebo in a randomized, single-blind, crossover design. [ C]-(+)-PHNO binding in the striatum and in the extra-striatal regions were compared between the 2 scans.
Acute alcohol administration did not significantly reduce [ C]-(+)-PHNO binding in either the limbic striatum (d = 0.64), associative striatum (d < 0.20), or the sensorimotor striatum (d < 0.15). Similarly, there were no changes in binding in the D -rich areas of the ventral pallidum (d = 0.53), substantia nigra (d < 0.15), or globus pallidus (d < 0.15). However, greater percent change in [ C]-(+)-PHNO binding (ΔBP ) between scans was related to lower blood alcohol levels.
Using the agonist radiotracer, [ C]-(+)-PHNO, our preliminary findings suggest that alcohol is not associated with robust changes in tracer binding in striatal or extra-striatal regions. However, we found that changes in [ C]-(+)-PHNO binding following alcohol are dependent on blood alcohol levels suggesting that increases in DA may occur at lower stimulating doses. The effect of lower doses of alcohol on DA warrants further investigation in a larger study.
先前探索急性酒精对多巴胺（DA）水平影响的正电子发射断层扫描（PET）研究结果并不一致，只有部分研究表明酒精激发后突触DA水平升高。D /D激动剂放射性示踪剂[ C]-(+)-丙基-六氢萘并恶嗪（[ C]-(+)-PHNO）对突触DA波动的敏感性高于先前使用的拮抗剂放射性示踪剂，原则上更适合对酒精诱导的DA变化进行成像。其对D受体的高亲和力还能够测量富含D的脑区（此前未被探索过）的变化。本研究的目的是调查酒精是否会降低纹状体及富含D的纹外区域中[ C]-(+)-PHNO的结合。
8名健康饮酒者按照随机、单盲、交叉设计，在饮酒和服用安慰剂后分别接受了2次[ C]-(+)-PHNO PET扫描。对两次扫描中纹状体及纹外区域的[ C]-(+)-PHNO结合情况进行比较。
急性酒精给药并未显著降低边缘纹状体（d = 0.64）、联合纹状体（d < 0.20）或感觉运动纹状体（d < 0.15）中[ C]-(+)-PHNO的结合。同样，腹侧苍白球（d = 0.53）、黑质（d < 0.15）或苍白球（d < 0.15）等富含D的区域的结合也没有变化。然而，两次扫描之间[ C]-(+)-PHNO结合的更大百分比变化（ΔBP）与较低的血液酒精水平相关。
使用激动剂放射性示踪剂[ C]-(+)-PHNO，我们的初步研究结果表明，酒精与纹状体或纹外区域中示踪剂结合的显著变化无关。然而，我们发现酒精后[ C]-(+)-PHNO结合的变化取决于血液酒精水平，这表明在较低刺激剂量下可能会发生DA增加。低剂量酒精对DA的影响值得在更大规模的研究中进一步调查。
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