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Rats were trained to discriminate nicotine (0.4 mg/kg SC) from saline in a standard two-bar operant conditioning procedure with food reinforcement. The response to nicotine was dose-related and at the ED50 of 0.14 mg/kg, plasma nicotine concentrations were similar to those reported previously for cigarette smokers who inhale. The nicotine analogues anabasine and cytisine increased nicotine-appropriate responding in a dose-related manner. Animals predominantly responded on the saline-associated lever when administered drugs from a range of pharmacological classes, even at doses that were sufficiently large to reduce the overall numbers of responses. The results confirm that the nicotine discriminative stimulus is highly specific. Previous work has shown anabasine and cytisine to be active at nicotinic-cholinergic binding sites in rat brain. The finding that there is some correlation between the behavioural effects of these compounds and their actions at the nicotine binding site may indicate that the nicotine cue is mediated through a cholinergic receptor.

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Acquisition of two-way avoidance by mice was slower with a light CS than with a buzzer CS, with punishment of intertrial responses than without punishment, and with a short CS-CS interval than with a long CS-CS interval (30 vs. 60 sec). Light-cued avoidance was little affected by shock level (.35-1.5 mA), whereas mice trained with the buzzer CS learned faster at 1.5 mA. Animals required to move away from light or toward light showed comparable rates of acquisition. Other CS, US, and apparatus variables (directionality of cue, maximal shock duration, and presence vs. absence of a central partition in the shuttlebox) interacted in a complex fashion with those already mentioned. This resulted in widely differing performances in what may superficially appear to be different versions of the same task. The differences in mouse and rat responses to some of the variables can contribute to an understanding of the interactions between organismic and test factors and the relative explanatory value of alternative avoidance models.