Retrograde conditioning of place preference and motor activity with cocaine in mice

Rationale: In order to improve understanding of the nature of drug-associated memory, the current studies addressed whether conditioned place preference (CPP) could develop under conditions in which there was a delay between presentation of context and drug exposure (i.e., retrograde or trace conditioning). Objectives: The objective was to assess development of CPP when cocaine or methamphetamine was injected simultaneously with exposure to a salient context (S+), or after delays differing in length. Methods: Dose response curves for conventional CPP were established using separate groups of Swiss-Webster mice injected with cocaine or methamphetamine just prior to S+ exposure. To assess the development of retrograde CPP, other groups received trace conditioning, where cocaine (15 mg/kg) or methamphetamine (0.5 mg/kg) was injected after a delay of 15, 60, 120, 180, 240, or 480 min following the end of the S+ session. Results: Mice receiving conventional CPP with cocaine or methamphetamine during S+ showed significant place preference. None of the groups receiving delayed methamphetamine showed significant CPP; however, CPP was evident in mice receiving cocaine after delays of up to 4 h following S+. In a separate study, delayed methamphetamine also did not result in significant place preference when presented in doses of 0.25 or 1 mg/kg. Conclusions: These results suggest that psychostimulant drug taking may be broadly generalized to context through retrograde association with events in recent memory, a factor that may contribute to drug-seeking and relapse following abstinence.