Pharmacology Biochemistry and Behavior, Vol. 66, No. 2, pp. 313–321, 2000 © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0091-3057/00/$–see front matter PII S0091-3057(00)00184-2 313 Effects of Cocaine and Morphine Under Mixed-Ratio Schedules of Food Delivery: Support for a Behavioral Momentum Analysis ALAN POLING, TOM BYRNE, LEEANN CHRISTIAN AND MARK G. LESAGE Western Michigan University, College of Arts and Sciences, Department of Psychology, Kalamazoo, MI 49008-5052 Received 9 July 1999; Revised 27 September 1999; Accepted 20 October 1999 POLING, A., T. BYRNE, L. CHRISTIAN AND M. G. LESAGE. Effects of cocaine and morphine under mixed- schedules of food delivery: Support for a behavioral momentum analysis. PHARMACOL BIOCHEM BEHAV 66(2) 313– 321, 2000.—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) sched- ules, 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 re- sponse rates stabilized. Finally, postchronic dose–response determinations were conducted. Both cocaine and morphine re- duced response rates at all FR values. Tolerance was consistently observed to the effects of morphine, but not to those of co- caine. 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. © 2000 Elsevier Science Inc. Tolerance Morphine Cocaine Mixed schedule Pigeons TOLERANCE occurs when the dose of a drug required to produce a given effect increases as a result of repeated expo- sure to that drug (21). That is, the dose–response curve shifts to the right as a result of chronic exposure. The rapidity and extent of tolerance development is influenced by several vari- ables, including the drug and response in question and the manner in which chronic exposure is arranged [e.g., (7)]. When drug effects on operant behavior are considered, the specific conditions under which behavior is maintained can strongly affect the development of tolerance [e.g., (31)]. For example, seven studies, which collectively evaluated five drugs in three species, provide substantial evidence that the amount of responding required for reinforcement, or “ef- fort,” influences tolerance (6,9,10,19,20,29,30). In these stud- ies, greater tolerance developed under relatively short fixed- ratio (FR) schedules than under relatively long FR schedules. This effect has been demonstrated, for example, with cocaine under conditions where FRs that differed in length appeared in a multiple schedule arrangement (9,10) and under condi- tions where FRs that differed in length were arranged for dif- ferent subjects (19). In both cases, the drug initially reduced response and reinforcement rates, and the greatest tolerance developed at the shortest ratio. Ratio size also has been dem- onstrated to influence the development of tolerance to the rate-reducing effects of morphine in pigeons responding un- der a multiple FR 5 FR 25 FR 125 schedule of food delivery, although some tolerance developed at each FR value (20). Under a multiple schedule, component schedules (e.g., FR 5, FR 25, FR 125) alternate, and each one is correlated with a different environmental stimulus (e.g., the key pecked by pi- geons might be red during the FR 5, green during the FR 25, and white during the FR 125). Requests for reprints should be addressed to A. Poling, Western Michigan Univeristy, College of Arts and Sciences, Department of Psychol- ogy, Kalamazoo, MI 59008-4500