A new progressive ratio schedule for support of morphine self-administration in opiate dependent rats

Psychopharmacology (Berl). 2003 Aug;168(4):387-96. doi: 10.1007/s00213-003-1442-x. Epub 2003 May 6.


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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Conditioning, Operant / drug effects*
  • Cues
  • Dose-Response Relationship, Drug
  • Infusions, Intravenous
  • Male
  • Morphine / administration & dosage*
  • Naloxone / administration & dosage
  • Opioid-Related Disorders / physiopathology*
  • Rats
  • Rats, Wistar
  • Reinforcement Schedule*
  • Self Administration / adverse effects
  • Substance Withdrawal Syndrome
  • Time Factors


  • Naloxone
  • Morphine