Temporal factors in drug discrimination: Experiments with nicotine.

The role of the presession interval (PI) in drug discrimination research has been studied in rats trained to discriminate nicotine from saline in a two-bar operant conditioning procedure. Different groups of rats were trained at different Pls, varying between 5 and 35 min, and tests were then carried out for qualitative and quantitative differences between the cues. There was complete generalization from nicotine cues trained at one time to tests carried out at other times. The sensitivity of the cues at different Pls to the nicotinic antagonist mecamylamine was very similar. Generalization to amphetamine was nearly complete when the nicotine cue was established with PI of 20-35 min and only partial when the PI for the nicotine was 5 min. Thus, there was no clear evidence for any qualitative difference between nicotine cues established with different PIs. However, the PI influenced quantitative aspects of the nicotine cue in a marked and complex manner. Increasing the PI during training produced a two- to three-fold decrease in the ED(50), whereas increasing the PI during testing produced a two- to three-fold increase in the ED(50). This shows that the effects of changing the PIs during training and testing were similar in magnitude but opposite in direction. These changes in ED(50) values can be explained by pharmacokinetic considerations in conjunction with knowledge of the role of training dose in the discrimination of nicotine. The quantitative sensitivity of the drug discrimination procedure can be substantially influenced by the choice of temporal parameters used in training and testing.