Abstract
Rationale
Rats develop preferences for places associated with the immediate rewarding effects of cocaine and aversions for places paired with the drug’s delayed negative effects. The motivation to seek cocaine should therefore depend upon the relative magnitude of these two opposing effects of the drug.
Objective
The current study tested this notion by assessing the relative persistence of the positive and negative associations formed between environmental cues and the immediate or delayed effects of cocaine.
Methods
Rats were administered 1.0 mg/kg intravenous cocaine and placed into a distinctive environment either immediately or 15-min after injection, alternating daily with pairings of a second environment with saline. After four drug-place and four saline-place pairings, rats were returned to their home cages for 1, 7, or 21 days after which a 15-min place preference test was conducted. In a second experiment, the effectiveness of a single reconditioning session (one drug-place and one saline-place pairing) to reactivate learned cocaine-place associations was assessed after 1 or 3 weeks of drug abstinence.
Results
Places associated with the immediate effects of cocaine were preferred (CPP), while places associated with the delayed effects of cocaine were avoided (CPA). The persistence of these effects differed with CPP remaining viable at 3 weeks of withdrawal, while CPA was no longer present after 1 week. Reconditioning with an additional cocaine-place pairing failed to reinstate the CPA.
Conclusions
Cue-induced “relapse” of cocaine-seeking behavior may be fueled in part by an increased persistence of positive relative to negative associations with drug-paired stimuli.
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Acknowledgments
The authors acknowledge, with gratitude, Dr. Osnat Ben-Shahar, Stephanie Waldroup, and Hilary Hammond for their assistance in various aspects of the project. This research was funded by NIDA grants DA05041 and DA033370 awarded to A.E.
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Su, ZI., Santoostaroam, A., Wenzel, J. et al. On the persistence of cocaine-induced place preferences and aversions in rats. Psychopharmacology 229, 115–123 (2013). https://doi.org/10.1007/s00213-013-3086-9
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DOI: https://doi.org/10.1007/s00213-013-3086-9