Holloway F A, King D A, Michaelis R C, Harland R D, Bird D C
Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Psychopharmacology (Berl). 1989;99(4):479-85. doi: 10.1007/BF00589895.
The effects of pre-session and post-session daily ethanol injections on the development and loss of tolerance to ethanol's effects on fixed ratio operant performance in rats was assessed using a cumulative dosing procedure. Daily pre-session ethanol administration produced a greater decrease in ethanol sensitivity than did daily post-session ethanol. Both tolerance effects persisted for at least 1 month after the chronic injection phase. No changes in ethanol sensitivity were apparent in the saline control group and no changes in estimated blood ethanol levels were found after the chronic treatments. The post-session ethanol groups displayed a performance decrement during the initial segment of the chronic injection period, but improved significantly across the chronic phase. These data suggest that some delayed effect of ethanol initially impaired performance but that tolerance to this ethanol effect also occurred and probably contributed to the decline in ethanol sensitivity seen in these groups. Compensatory learning as the mechanism for tolerance development in the pre-session and post-session ethanol groups was supported by the finding of no change in ethanol sensitivity in rats exposed to comparable daily ethanol without any concurrent operant task on which the direct, immediate, or indirect, delayed ethanol effects could operate.
采用累积给药程序，评估了每日在实验前和实验后注射乙醇对大鼠乙醇效应的耐受性发展和丧失以及对固定比率操作性行为表现的影响。每日在实验前给予乙醇比每日在实验后给予乙醇导致乙醇敏感性下降幅度更大。在慢性注射阶段后，两种耐受性效应至少持续1个月。生理盐水对照组中乙醇敏感性无明显变化，慢性处理后估计的血液乙醇水平也无变化。实验后给予乙醇的组在慢性注射期初始阶段表现下降，但在整个慢性阶段显著改善。这些数据表明，乙醇的某些延迟效应最初损害了行为表现，但对这种乙醇效应的耐受性也出现了，这可能导致了这些组中乙醇敏感性的下降。在没有任何同时进行的操作性任务（乙醇的直接、即时或间接、延迟效应可作用于该任务）的情况下，对每日接触等量乙醇的大鼠进行观察，发现其乙醇敏感性无变化，这支持了补偿性学习是实验前和实验后给予乙醇组耐受性发展机制的观点。
