Abstract
Rationale and objectives
In preliminary studies, we observed that opiate dependent rats self-administered only a small number of morphine injections under a PR (progressive ratio) schedule developed to study psychostimulant self-administration. Therefore, a new schedule was developed to support morphine self-administration by incrementing response requirements in a relatively gradual manner. The present study compared morphine self-administration under a commonly used PR schedule to self-administration maintained by our modified PR schedule.
Methods
After pretreatment with non-contingent morphine, rats acquired self-administration under fixed-ratio (FR) schedules of intravenous morphine delivery. Morphine-maintained behavior was evaluated under a standard PR schedule (termed "PR3–4", because the third response requirement was four lever presses), and our modified PR schedule (termed "PR9–4", because the ninth response requirement was four lever presses). The PR9–4 schedule was also evaluated for self-administration of morphine doses of 0.001–3.2 mg/kg per injection.
Results
The number of ratios completed for morphine self-administration on the PR9–4 schedule, but not the PR3–4 schedule, exceeded values obtained during extinction. Dose-related increases in completed ratios occurred for morphine self-administration on the PR9–4 schedule, with stable patterns emerging after three sessions. A relatively flat dose-response relationship was observed, which did not increase monotonically with morphine dose. Morphine self-administration on the PR9–4 schedule decreased mean inter-injection interval and prolonged the duration of responding during 6-h sessions.
Conclusions
In the present study, a schedule that incremented response requirement gradually (PR9–4) supported reliable self-administration across a range of morphine doses.
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Acknowledgements
This study was supported by a grant to K.G. from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs. The authors would like to thank the Midwest Biomedical Research Foundation of Kansas City Missouri for administrative support.
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Grasing, K., Li, N., He, S. et al. A new progressive ratio schedule for support of morphine self-administration in opiate dependent rats. Psychopharmacology 168, 387–396 (2003). https://doi.org/10.1007/s00213-003-1442-x
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DOI: https://doi.org/10.1007/s00213-003-1442-x