Reactivation of morphine conditioned place preference by drug priming: role of environmental cues and sensitization

Rationale: Relapse is a major characteristic of drug addiction and remains the primary problem in treating drug abuse. Despite a great deal of research, the exact factors that determine renewed drug-seeking and persistent craving for them remain unclear. Objective: The present study was designed to evaluate the role of environmental cues and behavioral sensitization in reactivation of place preference following long-term extinction of morphine conditioned place preference (CPP) in rats. Methods: After being injected with morphine and saline alternately for 6 days to induce morphine CPP, the rats were subjected to extinction of conditioning for 21 days. The rats were then administered various doses of morphine, heroin, or cocaine and confined in the previous drug- or saline-paired compartment. CPP was determined. Some rats were treated with scopolamine or naloxone prior to administration of these three drugs. Results: Morphine CPP disappeared following a 21-day extinction. A single injection of morphine, heroin, or cocaine evoked place preference for the previous drug-paired side. However, place preference for the previous vehicle-paired side was induced after the animals received a single injection of morphine, heroin or cocaine and confined to the previous vehicle-paired compartment. Administration of naloxone prior to drug treatment significantly attenuated the place preference induced by morphine or heroin, but had no significant effect on the place preference elicited by cocaine. Administration of the cholinergic antagonist scopolamine before morphine, heroin and cocaine inhibited the expression of place preference. Conclusions: Environment-related cues and behavioral sensitization play critical roles in the incentive motivation underlying drug-seeking behaviors.