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大鼠中孕烷醇酮与乙醇神经生理效应的比较。

Comparison of the neurophysiological effects of allopregnanolone and ethanol in rats.

作者信息

Slawecki C J, Walpole T, Purdy R H, Ehlers C L

机构信息

Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037, USA.

出版信息

Psychopharmacology (Berl). 2000 May;149(4):351-9. doi: 10.1007/s002139900365.

DOI:10.1007/s002139900365
PMID:10867962
Abstract

RATIONALE

The central nervous system actions of allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) and ethanol are at least partially mediated by modulation of gamma-aminobutyric acid (GABA)-A receptors. Although ethanol and allopregnanolone have similar behavioral effects, their macro-electrophysiological profiles have not been directly compared.

OBJECTIVE

The purpose of this study was to compare the effects of allopregnanolone and ethanol on the electroencephalogram (EEG) and event-related potentials (ERPs).

METHODS

Male Wistar rats were implanted with cortical and amygdalar electrodes. The rats were then administered allopregnanolone (0.0-10 mg/kg), ethanol (0.0-1.0 g/kg), or a combination of the two before recording.

RESULTS

Allopregnanolone and ethanol had similar effects on ERPs. When administered alone, both decreased cortical P1-N1 ERP amplitude by 25-50% and N1 amplitude in the amygdala by 75-80%. Combined administration of ethanol (0.50 g/kg) and allopregnanolone (5.0 mg/kg), doses which were ineffective alone, decreased N1 amplitude in the amygdala by 60%. Allopregnanolone and ethanol had dissimilar EEG effects. Allopregnanolone increased high frequency power in the cortex and amygdala by 25-30%. Ethanol decreased cortical and amygdalar power in the same high frequency bands by 25-45%. Allopregnanolone, but not ethanol, also shifted cortical frequency in the 32- to 50-Hz band. Combined administration of allopregnanolone and ethanol had no effect on EEG power but enhanced allopregnanolone's effect on cortical frequency.

CONCLUSIONS

These data suggest that allopregnanolone's macro-electrophysiological profile resembles barbiturates and benzodiazepines more than ethanol. Further, the interactions of allopregnanolone and ethanol appear complex, with multiple effects observed (enhancement or reversal) depending on the neurophysiological variable assessed.

摘要

理论依据

别孕烯醇酮(3α-羟基-5α-孕烷-20-酮)和乙醇对中枢神经系统的作用至少部分是通过调节γ-氨基丁酸(GABA)-A受体介导的。尽管乙醇和别孕烯醇酮具有相似的行为效应,但它们的宏观电生理特征尚未得到直接比较。

目的

本研究的目的是比较别孕烯醇酮和乙醇对脑电图(EEG)和事件相关电位(ERP)的影响。

方法

雄性Wistar大鼠植入皮质和杏仁核电极。然后在记录前给大鼠分别注射别孕烯醇酮(0.0 - 10mg/kg)、乙醇(0.0 - 1.0g/kg)或两者的组合。

结果

别孕烯醇酮和乙醇对ERP有相似的影响。单独给药时,两者均使皮质P1-N1 ERP波幅降低25 - 50%,杏仁核中N1波幅降低75 - 80%。乙醇(0.50g/kg)和别孕烯醇酮(5.0mg/kg)单独使用无效,但联合给药使杏仁核中N1波幅降低60%。别孕烯醇酮和乙醇对EEG的影响不同。别孕烯醇酮使皮质和杏仁核的高频功率增加25 - 30%。乙醇使相同高频波段的皮质和杏仁核功率降低25 - 45%。别孕烯醇酮(而非乙醇)还使32至50Hz频段的皮质频率发生偏移。别孕烯醇酮和乙醇联合给药对EEG功率无影响,但增强了别孕烯醇酮对皮质频率的影响。

结论

这些数据表明,别孕烯醇酮的宏观电生理特征与巴比妥类药物和苯二氮卓类药物更相似,而不是乙醇。此外,别孕烯醇酮和乙醇之间的相互作用似乎很复杂,根据所评估的神经生理变量观察到多种效应(增强或逆转)。

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