Hughes, C. E., Sigmon, S. C., Pitts, R. C., & Dykstra, L. A. (2005).
Morphine tolerance as a function of ratio schedule: Response requirement or unit price?
Journal of the Experimental Analysis of Behavior, 83, 281-296.
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.
Key words: morphine, fixed-ratio schedule, amount of reinforcement, tolerance,
unit price, key peck, pigeons