Rapid acquisition of a two-drug discrimination: time of day effect upon saline state.

Rats were rapidly trained to discriminate between 0.8 mg/kd d-amphetamine and 6 mg/kg pentobarbital in a two-lever food-motivated operant task by imposing the drug states from the earliest stage of training, i.e., at the initiation of shaping to lever-press. Once trained, rats were administered each of the training drugs and were allowed to lever press without reinforcement until 10 responses were made on the lever that was not their first choice lever selection. By employing this extended schedule of responding in extinction, the amphetamine-induced interoceptive cue was observed to produce equivalent perseverance as that produced by pentobarbital. However, the administration of saline, the non-drugged state, produced significantly more pentobarbital-appropriate responding than amphetamine-appropriate responding when tested during the daytime, whereas it produced random responding when tested during the night. The results suggest that the arousal state of the rat, a nocturnal species, may differentially influence saline tests in the daytime and in the night time.