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戒酒的酒精依赖女性中γ-氨基丁酸-苯二氮䓬受体水平:一项123I-碘美西泮单光子发射断层扫描研究的初步结果

Levels of gamma-aminobutyric acid-benzodiazepine receptors in abstinent, alcohol-dependent women: preliminary findings from an 123I-iomazenil single photon emission tomography study.

作者信息

Lingford-Hughes A R, Acton P D, Gacinovic S, Boddington S J, Costa D C, Pilowsky L S, Ell P J, Marshall E J, Kerwin R W

机构信息

Department of Psychological Medicine, Institute of Psychiatry, London, UK.

出版信息

Alcohol Clin Exp Res. 2000 Sep;24(9):1449-55.

Abstract

BACKGROUND

Although alcohol dependence in women is an increasing problem, little is known about the effects of alcohol on the female brain. Evidence from a few structural and functional neuroimaging studies suggests that the female brain may be more susceptible than the male brain to the harmful effects of alcohol. However, no in vivo studies of the neuropharmacology of alcohol dependence in women have been carried out. The aim of this preliminary study was to test the hypothesis that alcohol dependence in women is associated with greater reduction in gamma-aminobutyric acid (GABA)-benzodiazepine receptor levels than in men with an equivalent drinking history.

METHODS

We used single photon emission tomography and 123I-iomazenil to label the central GABA-benzodiazepine receptor and to compare semiquantified levels in 9 abstinent alcohol-dependent and 13 control women. These groups were further compared with equivalent male groups from a previous study.

RESULTS

There was a trend toward a reduction in GABA-benzodiazepine receptor levels in alcohol-dependent women, but this did not reach significance. These lower levels were seen primarily in the cerebellum, occipital lobes, and parietal cortex (left > right). This was in marked contrast with the pattern of reduction seen in the previous study of male dependence, where significant reductions were seen primarily in the frontal cortex.

CONCLUSIONS

Due to the semiquantitative analysis performed and the relatively small number of subjects in this study, which resulted in a nonsignificant trend, we can only comment on the differences in the pattern of lower levels of GABA-benzodiazepine receptors seen in alcohol dependence in men and women. Although we are not able to ascertain whether the female brain is more susceptible to the effects of alcohol, it appears that alcohol has a differential effect on the central GABA-benzodiazepine receptors in men and women. Recent animal evidence supports this hypothesis. Future studies should explore whether other neuropharmacological differences exist between men and women in alcohol dependence that could have implications for pharmacotherapy.

摘要

背景

尽管女性酒精依赖问题日益严重,但关于酒精对女性大脑的影响却知之甚少。一些结构和功能神经影像学研究的证据表明,女性大脑可能比男性大脑更容易受到酒精有害影响。然而,尚未开展关于女性酒精依赖神经药理学的体内研究。这项初步研究的目的是检验以下假设:与饮酒史相当的男性相比,女性酒精依赖与γ-氨基丁酸(GABA)-苯二氮䓬受体水平的更大降低有关。

方法

我们使用单光子发射断层扫描和123I-碘西尼来标记中枢GABA-苯二氮䓬受体,并比较9名戒酒的酒精依赖女性和13名对照女性的半定量水平。这些组与先前研究中的同等男性组进行了进一步比较。

结果

酒精依赖女性的GABA-苯二氮䓬受体水平有降低趋势,但未达到显著水平。这些较低水平主要见于小脑、枕叶和顶叶皮质(左侧>右侧)。这与先前男性依赖研究中观察到的降低模式形成鲜明对比,在该研究中,显著降低主要见于额叶皮质。

结论

由于本研究进行的是半定量分析且受试者数量相对较少,导致趋势不显著,我们只能评论在酒精依赖中男性和女性GABA-苯二氮䓬受体较低水平模式的差异。尽管我们无法确定女性大脑是否更容易受到酒精影响,但似乎酒精对男性和女性中枢GABA-苯二氮䓬受体有不同影响。最近的动物证据支持这一假设。未来的研究应探索在酒精依赖方面男性和女性之间是否存在其他可能对药物治疗有影响的神经药理学差异。

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