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

rationaleIn 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).

objectivesThe 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.

methodsDose 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.

resultsMice 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.

conclusionsThese 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.