Ginsburg Brett C, Martinez Gerardo, Friesenhahn Gregory, Javors Martin, Lamb R J
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA.
Physiol Behav. 2008 Jun 9;94(3):374-83. doi: 10.1016/j.physbeh.2008.01.026. Epub 2008 Feb 12.
Acute tolerance occurs when behavioral impairment is greater at a given blood ethanol concentration (BAC) on the ascending versus descending limb of the BAC-time curve following administration of a single dose of ethanol, however studies utilizing learned behaviors have not been widely reported. We assessed acute tolerance to single doses of ethanol in five Lewis rats responding under a fixed-ratio (FR8) schedule of food presentation. Response rates for food during 1-min components (ending 2, 4, 11, 18, 33, and 57 min after ethanol administration) were determined, and BAC was measured immediately after each component using a rat breathalyzer. Ethanol (0.4, 0.6, 0.8, and 1.2 g/kg, i.p.) produced dose-related decreases in responding for food that tended to recover over time for all but the highest dose tested. Similarly, dose-related increases in BAC were also observed. Using either an analysis that expressed impairment per unit BAC on the ascending limb versus the descending limb (by assessing the area under the curve (AUC) for behavior and BAC on each limb), the slope of the function that relates the behavioral effect to BAC (each expressed as percent maximum effect), or a variant of the Mellanby method (hysteresis), acute tolerance was observed following a dose of 0.4 g/kg ethanol. Though behavior appeared to recover on the descending limb following higher doses (especially 0.6 and 0.8 g/kg), acute tolerance to these doses was not present.
当在单次给予乙醇后，在血液乙醇浓度（BAC）-时间曲线的上升段与下降段，行为损伤在给定的BAC水平上更严重时，即发生急性耐受，然而利用习得行为的研究尚未得到广泛报道。我们评估了五只Lewis大鼠在固定比率（FR8）食物呈现时间表下对单剂量乙醇的急性耐受。测定了乙醇给药后1分钟时间段（结束于给药后2、4、11、18、33和57分钟）内的食物反应率，并在每个时间段结束后立即使用大鼠呼吸酒精含量测定仪测量BAC。乙醇（0.4、0.6、0.8和1.2 g/kg，腹腔注射）使食物反应呈剂量相关下降，除了测试的最高剂量外，其他剂量的反应率随着时间推移往往会恢复。同样，也观察到了BAC呈剂量相关增加。使用以下任何一种分析方法：比较上升段与下降段每单位BAC的损伤程度（通过评估各段行为和BAC的曲线下面积（AUC））、行为效应与BAC关系函数的斜率（均表示为最大效应百分比）或梅兰比方法的变体（滞后现象），在给予0.4 g/kg乙醇剂量后观察到了急性耐受。尽管在给予更高剂量（尤其是0.6和0.8 g/kg）后行为在下降段似乎有所恢复，但对这些剂量不存在急性耐受。
