Psychobiology Laboratories, Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190-3000 USA.
J Psychopharmacol. 1993 Jan;7(1 Suppl):52-62. doi: 10.1177/026988119300700109.
Sprague-Dawley rats were trained to discriminate between saline (SAL) and an ethanol-nicotine mixture (0.5 g/kg ethanol plus 0.5 mg/kg nicotine) administered 15 min prior to a 15-min drug discrimination training session under a FR-10 schedule of reinforcement. The mixture dose ratio was adjusted after training to obtain a drug mixture with which both individual drugs contributed about equally to the stimulus control (1.0 g/kg ethanol plus 0.3 mg/kg nicotine). The animals were then retrained for 32 sessions using this new mixture. After training, neither nicotine nor ethanol, when tested singly, engendered > 90% mixture-appropriate responding up to test doses that suppressed responding. Complete generalization occurred when the training doses of either nicotine or ethanol were administered in combination with various doses of the alternate drug element. (+)Nicotine, amphetamine and caffeine engendered dose-dependent increases in responses emitted on the mixture-appropriate lever. Pentobarbital and chloral hydrate only partially generalized to the training mixture. However, depressant/stimulant combinations of chloral hydrate+caffeine and pentobarbital+amphetamine produced complete generalization. The data suggest: (1) drug mixtures are not normally perceived as new entities distinct from their component elements; (2) training dose ratio may influence the characteristics of mixture discriminations; (3) stimulus element saliency may be a factor determining the nature of discriminative control by drug mixture cues; and (4) the ethanol-nicotine cue was most likely based on non-specific depressant/stimulant effects of these drugs.
斯普拉格-道利大鼠接受训练，以区分盐水（SAL）和乙醇-尼古丁混合物（0.5 克/公斤乙醇加 0.5 毫克/公斤尼古丁），在 15 分钟的药物辨别训练课程之前，根据 FR-10 强化时间表进行 15 分钟的药物辨别训练。在训练后，混合物剂量比进行了调整，以获得一种混合物，其中两种药物各自对刺激控制的贡献大致相等（1.0 克/公斤乙醇加 0.3 毫克/公斤尼古丁）。然后，动物使用这种新混合物重新训练 32 个疗程。训练后，单独测试尼古丁或乙醇时，均未引起>90%的混合物适当反应，直至抑制反应的测试剂量。当以各种剂量组合给予训练剂量的尼古丁或乙醇时，完全发生了概括。（+）尼古丁、安非他命和咖啡因会导致混合物适当杠杆上的反应呈剂量依赖性增加。戊巴比妥和水合氯醛仅部分概括为训练混合物。然而，水合氯醛+咖啡因和戊巴比妥+安非他命的抑制剂/兴奋剂组合产生了完全的概括。数据表明：（1）药物混合物通常不被视为与组成元素不同的新实体；（2）训练剂量比可能会影响混合物辨别特征；（3）刺激元素的显著性可能是决定药物混合物线索辨别控制性质的一个因素；（4）乙醇-尼古丁线索很可能基于这些药物的非特异性抑制剂/兴奋剂作用。
