A new progressive ratio schedule for support of morphine self-administration in opiate dependent rats.
OBJECTIVE
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.
Grasing
Kenneth
K
Research Service, Kansas City Veterans Affairs Medical Center, 4801 Linwood Boulevard, Kansas City, MO 64128, USA. kenneth.grasing@med.va.gov
Li
Ning
N
He
Shaunteng
S
Parrish
Christopher
C
Delich
John
J
Glowa
John
J
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000008:administration & dosage; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012646:Self Administration / Q000009:adverse effects; D013375:Substance Withdrawal Syndrome; D013997:Time Factors
D009270:Naloxone; D009020:Morphine