Rationale: Disruption of acquired drug-cue associations can effectively decrease relapse. The benefits of extinction training as opposed to abstinence have been reported. Timing of extinction trials is an important variable. Finding an effective extinction regimen can optimize addiction therapies. Objective: To determine the effects of different drug-free periods on cocaine-conditioned place preference (CPP) in rats that either did or did not receive non-reinforced exposure to drug-associated stimuli. Materials and methods: Male adolescent rats were trained for cocaine-CPP (5, 10, or 15 mg/kg, i.p.) in a biased manner for 8 days and then tested following different intervals. Results: Rats treated with 15 mg/kg cocaine displayed high and equal CPP on the first test, performed 1, 4, 7, or 14 days following conditioning. Expression of CPP during the test performed 1 day after conditioning was equal in the groups conditioned with 5, 10, or 15 mg/kg cocaine. When the interval before the first test was extended to 14 days, the group treated with 5 mg/kg did not show CPP. Rats treated with the three doses and tested repeatedly at 1, 7, and 14 days did not display CPP on the third test. CPP after treatment with 10 or 15 mg/kg cocaine was already extinguished in the second test but only for an interval of 1-14 days. Conclusions: Maintenance of CPP was evident at least 2 weeks after forced abstinence. Extinguished CPP can be obtained after a single extinction trial, performed close to original training and followed by prolonged abstinence. However, with low doses of cocaine, abstinence alone may be sufficient to disrupt drug-cue associations.
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Acknowledgments This research was supported by the Israel Science Foundation (grant no. 144/10) and the National Institute for Psychobiology in Israel founded by the Charles E. Smith family. R. Yaka is affiliated with the David R. Bloom Center for Pharmacy and the Brettler Center for Research in Molecular Pharmacology and Therapeutics, School of Pharmacy, The Hebrew University of Jerusalem. Dr. Poltyrev thanks the Israel Ministry of Absorption for financial support.