Criswell Hugh E, Ming Zhen, Kelm M Katherine, Breese George R
Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC 27599, USA.
J Pharmacol Exp Ther. 2008 Aug;326(2):596-603. doi: 10.1124/jpet.107.135418. Epub 2008 May 23.
Whereas ethanol has behavioral actions consistent with increased GABAergic function, attempts to demonstrate a direct enhancement of GABA-gated currents by ethanol have produced mixed results. Recent work has suggested that a part of the GABAergic profile of ethanol may result from enhanced GABA release from presynaptic terminals. The present study examines the effect of ethanol on GABA release in several brain regions to assess the regional nature of ethanol-induced GABA release. Whole-cell voltage clamp recording of spontaneous inhibitory postsynaptic currents (sIPSCs) from mechanically dissociated neurons and miniature inhibitory postsynaptic currents (mIPSCs) and paired-pulse ratio (PPR) from a slice preparation were used to quantify GABA release. Ethanol produced a concentration-dependent increase in the frequency of sIPSCs recorded from mechanically dissociated cerebellar Purkinje neurons and mIPSCs from substantia nigra neurons without having an effect on sIPSCs recorded from lateral septal or cerebrocortical neurons. This regional difference in the effect of ethanol on GABA release was confirmed with PPR recording from brain slices. These data indicate that ethanol can act on presynaptic terminals to increase GABA release in some brain regions while having little or no effect on GABA release in others. This regional difference is consistent with earlier in vivo studies in which ethanol affected neural activity and sensitivity to GABA in some, but not all, brain sites.
虽然乙醇具有与增强GABA能功能相一致的行为作用，但试图证明乙醇直接增强GABA门控电流的研究结果却喜忧参半。最近的研究表明，乙醇的部分GABA能特性可能源于突触前终末GABA释放的增强。本研究检测了乙醇对多个脑区GABA释放的影响，以评估乙醇诱导的GABA释放的区域特性。通过对机械分离神经元的自发性抑制性突触后电流（sIPSCs）进行全细胞电压钳记录，以及对脑片制备中的微小抑制性突触后电流（mIPSCs）和双脉冲比率（PPR）进行记录，来量化GABA释放。乙醇使机械分离的小脑浦肯野神经元记录到的sIPSCs频率以及黑质神经元记录到的mIPSCs频率呈浓度依赖性增加，而对从外侧隔区或大脑皮质神经元记录到的sIPSCs没有影响。通过脑片的PPR记录证实了乙醇对GABA释放影响的这种区域差异。这些数据表明，乙醇可作用于突触前终末，在某些脑区增加GABA释放，而在其他脑区对GABA释放几乎没有影响或没有影响。这种区域差异与早期的体内研究一致，在这些研究中，乙醇在一些但不是所有脑区影响神经活动和对GABA的敏感性。
