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

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.