The discriminative stimulus properties of an ethanol-nicotine mixture in rats

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.