Morphine tolerance as a function of ratio schedule: response requirement or unit price?
Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, l-methadone, and cocaine dose-dependently decreased overall response rates in each of the components. When a rate decreasing dose of morphine was administered daily, tolerance, as measured by an increase in the dose that reduced response rates to 50% of control (i.e., the ED50 value), developed in each of the components; however, the degree of tolerance was smallest in the fixed-ratio 90 component (i.e., the ED50 value increased the least). When the l-methadone dose-effect curve was redetermined during the chronic morphine phase, the degree of cross-tolerance conferred to l-methadone was similar across components, suggesting that behavioral variables may not influence the degree of cross-tolerance between opioids. During the chronic phase, the cocaine dose-effect curve shifted to the right for 2 pigeons and to the left for 1 pigeon, which is consistent with predictions based on the lack of pharmacological similarity between morphine and cocaine. When the morphine, l-methadone, and cocaine dose-effect curves were redetermined after chronic morphine administration ended, the morphine and l-methadone ED50s replicated those obtained prior to chronic morphine administration. The morphine data suggest that the fixed-ratio value (i.e., the absolute output) determines the degree of tolerance and not the unit price.
Hughes
Christine E
CE
Department of Psychology, University of North Carolina Wilmington, 601 S. College Road, Wilmington, North Carolina 28403-5612, USA. hughesc@uncw.edu
Sigmon
Stacey C
SC
Pitts
Raymond C
RC
Dykstra
Linda A
LA
D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D010856:Columbidae; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D008691:Methadone / Q000008:administration & dosage / Q000494:pharmacology; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology
D018765:Dopamine Uptake Inhibitors; D009294:Narcotics; D009020:Morphine; D003042:Cocaine; D008691:Methadone