Timing of conditioned responding in a nicotine locomotor conditioning preparation: manipulations of the temporal arrangement between context cues and drug administration.

Using a locomotor conditioning preparation, we examined whether manipulating time between exposure to distinct environmental cues and nicotine administration affected conditioned responding. Rats that received nicotine (0.42 mg/kg base) immediately before placement in an environment for 30 min on eight separate occasions displayed hyperactivity relative to controls in a subsequent injection/drug-free test. This conditioned hyperactivity was weaker if nicotine was administered 15 min before environment exposure. Conditioning was not evidenced when nicotine was administered 15 min after placement or upon removal from the environment. In a follow-up experiment, rats received 45 min in the environment; nicotine was administered 15 min after placement. This group showed conditioning that was localized to the last two-thirds of a 45 min test indicating that a 15 min delay did not prevent conditioning given 30 min of environment/nicotine overlap. This apparent timing of conditioned responding was not due to increasing environment exposure to 45 min. Further, a state-dependent environmental familiarization account of locomotor hyperactivity during testing was eliminated by the finding that rats displayed temporally specific increases in activity on the test day despite the fact that the context was previously experienced without drug for 15 min on eight consecutive days.