Conditioned drug reward enhances subsequent spatial learning and memory in rats

Chronic exposure to drugs of abuse alters neural processes that normally promote learning and memory. A context that is repeatedly paired with reinforcing drugs will acquire secondary reinforcing properties (conditioned reward). However, the effects of conditioned reward on spatial learning are unknown. Using the conditioned place preference procedure and Morris water maze task, we examined the role of conditioned reward or aversion in spatial learning. Groups of rats acquired morphine (10 mg/kg), cocaine (10 mg/kg), or oral sucrose (15%) conditioned place preference (CPP). Another group of morphine-dependent rats acquired conditioned place aversion (CPA) to a context paired with precipitated opiate withdrawal induced by naloxone injections (1 mg/kg). To examine the role of conditioned reward or aversion in spatial learning, rats were then exposed to the previously morphine-, cocaine-, sucrose- or naloxone-paired context for 10 min before training of spatial learning in the Morris water maze. Exposure to the morphine- or cocaine-paired but not the sucrose- or the naloxone-paired context decreased the latency to find the platform in the Morris water maze test. Our results provide the first evidence that conditioned drug reward promotes spatial learning. We speculate that this enhancement of spatial learning by the drug-paired context may promote contextual-cue-induced relapse to drug taking by facilitating exploratory drug-seeking behaviors.