Fixed-ratio size as a determinant of tolerance to cocaine

Abstract

Six studies, examining five drugs in three species, have demonstrated that tolerance development is impaired under relatively long fixed-ratio (FR) schedules compared with relatively short FR schedules. One such study demonstrated that substantial tolerance to the rate-reducing effects of cocaine in pigeons developed under the FR 5 and 25 components of a multiple schedule of food delivery, but little or no tolerance developed under the FR 125 component. The present study examined the acute and chronic effects of cocaine in three groups of pigeons. One group was exposed to a simple FR 5 schedule of food delivery, a second to a simple FR 125 schedule of food delivery, and a third to a simple FR 125 schedule that alternated across sessions with a multiple FR 125 FR 250 schedule. When administered acutely, cocaine (1-10mg/kg) produced dose-dependent rate decreases under all schedules. With chronic exposure to 5.56mg/kg cocaine, tolerance clearly developed under the FR 5 schedule. Evidence of tolerance under the FR 125 schedule was equivocal, but strongest when that schedule alternated with an FR 250 component under a multiple schedule arrangement. There was no consistent evidence of tolerance under the FR 250 component. These results suggest that, although the development of tolerance under an FR schedule may be affected by exposure to a longer schedule, tolerance to cocaine does not develop readily under "long" FR schedules, regardless of the context in which they appear.