Conditioned place preference: what does it add to our preclinical understanding of drug reward?

Rationale: Among the various experimental protocols that have been used to measure drug reward in laboratory animals, conditioned place preference (CPP) has been one of the most popular. However, a number of controversial issues have surrounded the use of this experimental protocol. Objective: The present review provides a theoretical overview of some critical issues relevant to CPP. The advantages and limitations of CPP are also covered. Results: Based on modern and traditional theoretical formulations of Pavlovian conditioning, CPP appears to reflect a preference for a context due to the contiguous association between the context and a drug stimulus. Within this theoretical framework, it seems clear that CPP measures a learning process that is fundamentally distinct from drug self-administration. The main advantages of CPP are that it: (1) tests animals in a drug-free state; (2) is sensitive to both reward and aversion; (3) allows for simultaneous determination of CPP and locomotor activity; (4) is adaptable to a variety of species; (5) typically yields dose-effect curves that are monophasic rather than biphasic; and (6) has utility in probing the neural circuits involved in drug reward. The main limitations of CPP are that it: (1) is subject to interpretation based on the notion of novelty seeking; (2) is cumbersome for providing the graded dose-effect curves needed for answering some pharmacological questions; (3) is difficult to interpret when animals prefer one context prior to drug conditioning; and (4) lacks face validity as an experimental protocol of drug reward in humans. Conclusion: Despite some limitations, CPP provides unique information about the rewarding effect of contextual cues associated with a drug stimulus.