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MORPHINE TOLERANCE AS A FUNCTION OF RATIO SCHEDULE: RESPONSE REQUIREMENT OR UNIT PRICE?
Author(s) -
Hughes Christine E.,
Sigmon Stacey C.,
Pitts Raymond C.,
Dykstra Linda A.
Publication year - 2005
Publication title -
journal of the experimental analysis of behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.75
H-Index - 61
eISSN - 1938-3711
pISSN - 0022-5002
DOI - 10.1901/jeab.2005.35-04
Subject(s) - morphine , methadone , ed50 , reinforcement , drug tolerance , self administration , medicine , anesthesia , pharmacology , toxicology , mathematics , psychology , biology , social psychology , receptor
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 ED 50 value), developed in each of the components; however, the degree of tolerance was smallest in the fixed‐ratio 90 component (i.e., the ED 50 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 ED 50 s 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.