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  • Title: A new progressive ratio schedule for support of morphine self-administration in opiate dependent rats.
    Author: Grasing K, Li N, He S, Parrish C, Delich J, Glowa J.
    Journal: Psychopharmacology (Berl); 2003 Aug; 168(4):387-96. PubMed ID: 12732925.
    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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