Regional brain metabolic response to lorazepam in subjects at risk for alcoholism.
Regional brain metabolic response to lorazepam in subjects at risk for alcoholism.
复制标题
有酒精中毒风险的受试者对劳拉西泮的区域脑代谢反应。
DOI：
10.1111/j.1530-0277.1995.tb01539.x
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Wolf,AP
中科院分区：
文献类型：
--
作者：
Volkow,ND;Wang,GJ;Begleiter,H;Hitzemann,R;Pappas,N;Burr,G;Pascani,K;Wong,C;Fowler,JS;Wolf,AP
在酒精中毒高危人群中观察到的对酒精注射的钝性反应背后的机制尚不清楚，可能涉及GABA-苯二氮卓类受体。这项研究的目的是调查酒精中毒高危人群是否存在脑部GABA-苯二氮卓类受体功能异常。本研究用正电子发射断层扫描和2-脱氧-2[18F]氟-d-葡萄糖测定了30μg/kg(Iv)劳拉西潘对有酒精中毒家族史阳性(FP)受试者(n=12)的局部脑葡萄糖代谢的影响，并与有酗酒家族史阴性(FN)受试者(n=21)进行了比较。基线时，FP受试者的小脑代谢低于FN。劳拉西潘降低了全脑的葡萄糖代谢，FP受试者在皮质和皮质下对FN的反应相似，但FP在小脑表现出迟钝的反应。劳拉西潘引起的小脑代谢改变与其运动效应有关。FP患者小脑基线代谢下降，以及对劳拉西潘激发的小脑反应迟钝，可能反映了小脑中苯二氮卓类-GABA受体活性的紊乱。这些变化可能解释了FP受试者对酒精和苯二氮卓类药物运动效应敏感性降低的原因。
The mechanisms underlying the blunted response to alcohol administration observed in subjects at risk for alcoholism are poorly understood and may involve GABA‐benzodiazepine receptors. The purpose of this study was to investigate if subjects at risk for alcoholism had abnormalities in brain GABA‐benzodiazepine receptor function. This study measured the effects of 30 μg/kg (iv) of lorazepam, on regional brain glucose metabolism using positron emission tomography and 2‐deoxy‐2[18F]fluoro‐d‐glucose in subjects with a positive family history for alcoholism (FP) (n= 12) and compared their response with that of subjects with a negative family history for alcoholism (FN) (n= 21). At baseline, FP subjects showed lower cerebellar metabolism than FN. Lorazepam decreased whole‐brain glucose metabolism, and FP subjects showed a similar response to FN in cortical and subcortical regions, but FP showed a blunted response in cerebellum. Lorazepam‐induced changes in cerebellar metabolism correlated with its motor effects. The decreased cerebellar baseline metabolism in FP as well as the blunted cerebellar response to lorazepam challenge may reflect disrupted activity of benzodiazepine‐GABA receptors in cerebellum. These changes could account for the decreased sensitivity to the motor effects of alcohol and benzodiazepines in FP subjects.