Tolerance occurs when the dose-response curve for a given drug shifts rightward as a result of chronic exposure to that drug. Tolerance is important when drugs are used therapeutically, and it also plays a role in drug abuse. For example, tolerance is included by the American Psychiatric Association (1987) as a defining characteristic of psychoactive substance abuse disorders. The development of tolerance under a given drug regimen appears to be influenced by a range of environmental variables, many of which are understood incompletely. One such variable is response effort. Seven published studies have demonstrated that tolerance to the rate-reducing effects of psychoactive drugs, including cocaine and morphine, developed less readily under relatively long fixed-ratio schedules of food delivery than under shorter fixed-ratio schedules. These data suggest that the """"""""effort"""""""" required for reinforcement modulated, in part, the development of tolerance. The proposed studies, which will use pigeons as subjects, are intended to provide a detailed examination of response effort and related variables as determinants of tolerance to the effects of cocaine and morphine on schedule-controlled behavior. Three sets of studies are proposed. One set is intended to examine the feasibility of using PR schedules to assess the role of effort in modulating drug action and to compare the development of tolerance at comparable ratios arranged under PR and FR schedules. A second set is designed to separate the effects of effort per se from those of another variable, relative reinforcement loss, that may affect the development of tolerance. A third set will compare the development of tolerance under schedules that have equal average response requirements, but differ with respect to the actual ratios arranged. If the effects of cocaine or morphine prove to be truly effort-dependent, effort will need to be added to the list of variables that influence how operant behavior is affected by a given drug and dose. Although that list is already relatively long, the behavioral effects of abused and medicinal drugs cannot be understood fully until it is complete.
