Holloway F A, Bird D C, Holloway J A, Michaelis R C
Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center Oklahoma City 73190.
Pharmacol Biochem Behav. 1988 Jan;29(1):105-13. doi: 10.1016/0091-3057(88)90282-1.
Dose-effect analyses were used to monitor the development of tolerance for ethanol's effects on FR30 operant performance in rats under different conditions of chronic ethanol exposure: (a) pre-session ethanol injections (PRE) vs. post-session ethanol injections (POST) in Experiment 1; and (b) an ethanol liquid diet (ED) vs. a control diet (CD) in Experiment 2. The PRE and ED groups developed tolerance at the conclusion of the chronic regimens, which declined by six months but not to baseline levels. These data suggest that tolerance results from learned compensatory adjustments (through intoxicated practice) to ethanol's disruptive effects. The POST, but not the CD, group developed a progressively increasing degree of tolerance after several ethanol challenge tests. These results suggest that some threshold level of passive ethanol exposure in the POST group interacted with their limited intoxicated practice. Finally, the tolerance developed under intoxicated practice conditions did not appear to reflect a generalized tolerance to rate-reducing properties of drugs, changes in ethanol kinetics, or age-related changes.
剂量效应分析用于监测在不同慢性乙醇暴露条件下，大鼠对乙醇对FR30操作性行为表现影响的耐受性发展情况：(a) 实验1中，会话前乙醇注射（PRE）与会话后乙醇注射（POST）；以及(b) 实验2中，乙醇液体饲料（ED）与对照饲料（CD）。PRE组和ED组在慢性给药方案结束时产生了耐受性，这种耐受性在六个月后下降，但未降至基线水平。这些数据表明，耐受性是通过（醉酒状态下的）学习性代偿调整对乙醇的干扰作用产生的。POST组而非CD组在多次乙醇激发试验后产生了逐渐增强的耐受性。这些结果表明，POST组中被动乙醇暴露的某些阈值水平与其有限的醉酒状态下的练习相互作用。最后，在醉酒状态下的练习条件下产生的耐受性似乎并不反映对药物降低速率特性的普遍耐受性、乙醇动力学的变化或与年龄相关的变化。
