Svetlana Semenova1, Athina Markou2. 1. Department of Neuropharmacology, CVN-7, The Scripps Research Institute. 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, USA. 2. Department of Neuropharmacology, CVN-7, The Scripps Research Institute. 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, USA. amarkou@scripps.edu.
Abstract
RATIONALE: Cocaine abstinence symptoms and conditioned stimuli (CSs) previously associated with cocaine administration are postulated to contribute to relapse to drug taking in humans. OBJECTIVE: The present study assessed the role of both non-contingent CS presentation and experimenter-imposed extended cocaine-free periods on cocaine-seeking behavior in rats. METHODS: A fixed interval (FI) second-order schedule of intravenous cocaine (0.5 mg/infusion) reinforcement of the type FI 15 min (fixed ratio 8:S) was used. RESULTS: Non-contingent CS presentation before exposure to a cocaine binge had no effect on responding under the second-order schedule of reinforcement for cocaine after 23 h of no access to cocaine. By contrast, six non-contingent presentations of the CS during a 1-min period before the test session increased the number of responses in both no-binge (daily 2-h sessions, five infusions) and binge (two 12-h overnight sessions; maximum 48 infusions) exposed rats on day 7 of the cocaine-free period compared to no-binge- and binge-exposed rats that were not presented with the CSs. On day 30 of the cocaine-free period, only binge-exposed rats presented with the CSs exhibited a tendency for increased level of responding. CONCLUSIONS: The results indicated that non-contingent CS presentation had no effect after 23 h of no access to cocaine, increased drug-seeking behavior on day 7 of the cocaine-free period independent of binge exposure, and a strong tendency to increase drug-seeking behavior only in binge-exposed rats, on day 30 of the cocaine-free period, illustrating the interactive effects of conditioned stimuli with the extended cocaine-free period.
RATIONALE: Cocaine abstinence symptoms and conditioned stimuli (CSs) previously associated with cocaine administration are postulated to contribute to relapse to drug taking in humans. OBJECTIVE: The present study assessed the role of both non-contingent CS presentation and experimenter-imposed extended cocaine-free periods on cocaine-seeking behavior in rats. METHODS: A fixed interval (FI) second-order schedule of intravenous cocaine (0.5 mg/infusion) reinforcement of the type FI 15 min (fixed ratio 8:S) was used. RESULTS: Non-contingent CS presentation before exposure to a cocaine binge had no effect on responding under the second-order schedule of reinforcement for cocaine after 23 h of no access to cocaine. By contrast, six non-contingent presentations of the CS during a 1-min period before the test session increased the number of responses in both no-binge (daily 2-h sessions, five infusions) and binge (two 12-h overnight sessions; maximum 48 infusions) exposed rats on day 7 of the cocaine-free period compared to no-binge- and binge-exposed rats that were not presented with the CSs. On day 30 of the cocaine-free period, only binge-exposed rats presented with the CSs exhibited a tendency for increased level of responding. CONCLUSIONS: The results indicated that non-contingent CS presentation had no effect after 23 h of no access to cocaine, increased drug-seeking behavior on day 7 of the cocaine-free period independent of binge exposure, and a strong tendency to increase drug-seeking behavior only in binge-exposed rats, on day 30 of the cocaine-free period, illustrating the interactive effects of conditioned stimuli with the extended cocaine-free period.
Authors: Raveendra-Panickar Dhanya; Shyama Sidique; Douglas J Sheffler; Hilary Highfield Nickols; Ananda Herath; Li Yang; Russell Dahl; Robert Ardecky; Svetlana Semenova; Athina Markou; P Jeffrey Conn; Nicholas D P Cosford Journal: J Med Chem Date: 2010-12-14 Impact factor: 7.446
Authors: Xinchun Jin; Svetlana Semenova; Li Yang; Robert Ardecky; Douglas J Sheffler; Russell Dahl; P Jeffrey Conn; Nicholas D P Cosford; Athina Markou Journal: Neuropsychopharmacology Date: 2010-06-16 Impact factor: 7.853