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Place conditioning is widely used to study the conditioned rewarding effects of drugs. In the standard version, one reward (cocaine) is compared with no reward (saline). A modified variant of this task, 'reference-conditioning' procedure, compares two potentially rewarding stimuli (high vs. low cocaine dose). There has been little research on the utility of this procedure. Experiment 1 used the standard protocol with saline administered before confinement to the reference compartment of a place conditioning chamber. On alternate days, saline, 2.5, 5, 7.5, 10, or 20 mg/kg cocaine was administered before confinement to the opposite compartment. In experiments 2 and 3, reference-compartment saline was replaced with 5 and 7.5 mg/kg cocaine, respectively. Relative to saline, 7.5-20 mg/kg cocaine had comparable conditioned rewarding effects (i.e. similar increase in time in paired compartment). When cocaine replaced saline, there was competition at doses lower than 7.5 mg/kg. Rats that received 7.5 versus 2.5 mg/kg spent similar time in each compartment, indicating competition. Competition was not seen with 5 versus 20 mg/kg; preference was for the 20 mg/kg compartment. Experiment 4 showed that the competition at 2.5 mg/kg was not due to reward sensitization. The reference-conditioning procedure has increased the sensitivity for measuring associatively motivated choice behavior.

Reference place conditioning procedure with cocaine: increased sensitivity for measuring associatively motivated choice behavior in rats