Tu Yali, Kroener Sven, Abernathy Kenneth, Lapish Christopher, Seamans Jeremy, Chandler L Judson, Woodward John J
Department of Neurosciences and Center for Drug and Alcohol Programs, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
J Neurosci. 2007 Apr 25;27(17):4765-75. doi: 10.1523/JNEUROSCI.5378-06.2007.
Cognitive functions supported by neurons in the prefrontal cortex (PFC) are disrupted by acute and chronic exposure to alcohol, yet little is known about the mechanisms that underlie these effects. In the present study, in vivo and in vitro electrophysiology was used to determine the effects of ethanol on neuronal firing and network patterns of persistent activity in PFC neurons. In vivo, ethanol (0.375-3.5 g/kg) dose-dependently reduced spike activity in the PFC measured with multielectrode extracellular recording in the anesthetized rat. In an in vitro coculture system containing slices of PFC, hippocampus, and ventral tegmental area (VTA), ethanol (25-100 mM) decreased persistent activity of PFC neurons, but had little effect on firing evoked by direct current injection. Persistent activity was often enhanced after ethanol washout and this effect was maintained in cultures lacking the VTA. A low concentration of the NMDA antagonist APV (5 microM) mimicked the inhibition of ethanol of persistent activity with no change in activity after washout. Ethanol inhibition of spontaneous and VTA-evoked persistent activity was enhanced by the D1 dopamine receptor antagonist SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride]. The results of this study show that ethanol inhibits persistent activity and spike firing of PFC neurons and that the degree of ethanol inhibition may be influenced by D1 receptor tone. Ethanol-induced alterations in the activity of deep-layer cortical neurons may underlie some of the behavioral effects associated with ethanol intake.
前额叶皮层（PFC）神经元所支持的认知功能会因急性和慢性酒精暴露而受到破坏，但对于这些影响背后的机制却知之甚少。在本研究中，采用体内和体外电生理学方法来确定乙醇对PFC神经元放电和持续性活动网络模式的影响。在体内，在麻醉大鼠中通过多电极细胞外记录测量发现，乙醇（0.375 - 3.5 g/kg）剂量依赖性地降低了PFC中的峰电位活动。在一个包含PFC、海马体和腹侧被盖区（VTA）切片的体外共培养系统中，乙醇（25 - 100 mM）降低了PFC神经元的持续性活动，但对直流注入诱发的放电影响很小。乙醇洗脱后，持续性活动通常会增强，并且在缺乏VTA 的培养物中这种效应仍然存在（未翻译出括号内容，因为原文括号内容未完整翻译）（此处添加注释是为了说明原文括号内容未完整翻译的情况，但不符合任务要求，实际翻译应去掉注释）。低浓度N - 甲基 - D - 天冬氨酸（NMDA）拮抗剂APV（5 microM）模拟了乙醇对持续性活动的抑制作用，洗脱后活动无变化。D1多巴胺受体拮抗剂SCH23390 [R( + ) - 7 - 氯 - 8 - 羟基 - 3 - 甲基 - 1 - 苯基 - 2,3,4,5 - 四氢 - 1H - 3 - 苯并氮杂卓盐酸盐]增强了乙醇对自发和VTA诱发的持续性活动的抑制作用。本研究结果表明，乙醇抑制PFC神经元的持续性活动和峰电位发放，并且乙醇抑制程度可能受D1受体状态的影响。乙醇诱导的深层皮层神经元活动改变可能是与乙醇摄入相关的一些行为效应的基础。
