Abstract
Rationale and objective
We sought to examine the impact of differing cocaine administration schedules and dosing on the magnitude of cocaine conditioned place preference (CPP), extinction, and stress- and cocaine-induced reinstatement of CPP.
Methods
First, in C57Bl/6J mice, we investigated whether total cocaine administration or pattern of drug exposure could influence the magnitude of cocaine CPP by conditioning mice with a fixed-low dose (FL; 7.5 mg/kg; total of 30 mg/kg), a fixed-high dose (FH; 16 mg/kg; total of 64 mg/kg), or an ascending dosing schedule (Asc; 2, 4, 8, and 16 mg/kg; total of 30 mg/kg). Next, we investigated if cocaine or saline is more effective at extinguishing preference by reconditioning mice with either a descending dosing schedule (Desc; 8, 4, 2, and 1 mg/kg) or saline. Finally, we examined if prior conditioning and reconditioning history alters stress (~2–3-min forced swim test) or cocaine-induced (3.5 mg/kg) reinstatement.
Results
We replicated and extended findings by Itzhak and Anderson (Addict. Biol. 17(4): 706–16, 2011) demonstrating that Asc conditioning produces a greater CPP than either the FL or FH conditioning schedules. The magnitude of extinction expressed was similar in the Desc reconditioned and saline groups. Moreover, only the saline, and not the Desc reconditioned mice, showed stress and cocaine-induced reinstatement of CPP.
Conclusions
Our results suggest that the schedule of cocaine administration during conditioning and reconditioning can have a significant influence on the magnitude of CPP and extinction of preference and the ability of cocaine or a stressor to reinstate CPP.
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Acknowledgments
The behavioral data presented in this manuscript were generated at the Vanderbilt Murine Neurobehavioral Laboratory (http://kc.vanderbilt.edu/mnlcore/). We would like to thank Dr. John Allison for his generous assistance and expertise. This work was supported by National Institutes of Health grants NS07491 and MH065215-08 (KLC) and AA019455 AND DA019112 (DGW).
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All authors report no biomedical financial interests or potential conflicts of interest.
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Kelly L. Conrad and Katherine M. Louderback contributed equally to this work.
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Conrad, K.L., Louderback, K.M., Milano, E.J. et al. Assessment of the impact of pattern of cocaine dosing schedule during conditioning and reconditioning on magnitude of cocaine CPP, extinction, and reinstatement. Psychopharmacology 227, 109–116 (2013). https://doi.org/10.1007/s00213-012-2944-1
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DOI: https://doi.org/10.1007/s00213-012-2944-1