Fixed-ratio size as a determinant of the development of tolerance to morphine.

The acute and chronic effects of morphine were examined in pigeons exposed to a multiple schedule with fixed-ratio 5, 25, and 125 components. Acute exposure to morphine (0.56-10.0 mg/kg) resulted in rate reductions under each component when the dose was 1 mg/kg or higher. With chronic exposure to 5.6 mg/kg, tolerance to the rate-reducing effects of morphine was evident under each fixed-ratio component. The development of tolerance was determined to some extent by fixed-ratio size, a result similar to earlier findings with cocaine.