Effects of cocaine and morphine under mixed-ratio schedules of food delivery: support for a behavioral momentum analysis.

Previous studies have shown that ratio size influenced the development of tolerance under simple and multiple schedules, but not under progressive-ratio (PR) schedules. PR schedules share certain features with mixed-ratio (MR) schedules, and pilot data suggested that ratio size fails to modulate tolerance to cocaine or morphine under MR schedules. The present study examined more comprehensively the pre- and postchronic effects of cocaine and (in separate birds) morphine under MR schedules with fixed-ratio (FR) 5 and FR 95, FR 25 and FR 75, and FR 50 and FR 50 components. Acute doses of cocaine and morphine initially were given in an ascending series (beginning with 0.56 mg/kg) until responding was reduced to near-zero levels. Chronic (daily) dosing with a dose that reduced, but did not eliminate, responding then occurred until response rates stabilized. Finally, postchronic dose-response determinations were conducted. Both cocaine and morphine reduced response rates at all FR values. Tolerance was consistently observed to the effects of morphine, but not to those of cocaine. With both drugs the degree of tolerance observed did not vary as a function of FR value. These findings, like those obtained under PR schedules, indicate that ratio size does not always modulate drug tolerance. A behavioral momentum analysis of drug action appears to account for whether or not ratio size modulates tolerance, and such an analysis is provided.