The Reference-Dose Place Conditioning Procedure Yields a Graded Dose-Effect Function

Abstract

A major criticism of the place conditioning procedure for studying conditioned drug reward is that it is relatively insensitive to large quantitative shifts in drug dose (i.e., dose effects are all or none). Experiment 1 demonstrated this lack of sensitivity using a wide range of intravenous (IV) cocaine doses (0.1, 0.3, 0.45, 0.6, 0.9, or 1.2 mg/kg). Rats had cocaine repeatedly paired with one distinct end compartment of a 3 compartment apparatus; vehicle was administered in the other end compartment. In a subsequent drug-free choice test, the 0.45 to 1.2 mg/kg doses of cocaine conditioned a place preference. The magnitude of the effect did not differ. Experiment 2 used a modified version of this standard place conditioning method. In this alternative method termed reference-dose procedure, a fixed dose of cocaine (reference dose) was repeatedly paired with one end compartment (i.e., 0.45 mg/kg); the comparison dose of cocaine was administered in the other end compartment (vehicle, 0.6, or 1.2 mg/kg). Preference for the comparison-dose compartment increased with dose—a graded doseeffect curve. In contrast to the standard procedure, the reference-dose procedure revealed that the conditioned rewarding effect of 1.2 mg/kg of cocaine was greater than that of 0.45 mg/kg. This increase in sensitivity to conditioned reward with the reference-dose procedure will likely increase the utility of the place conditioning method as a preclinical model, as well as a procedure for studying processes mediating associatively-motivated choice behavior.