Tolerance to effects of morphine without cross tolerance to effects of clonidine on schedule-controlled behavior of pigeons.

Schedule-controlled responding was maintained under a multiple fixed-interval, fixed-ratio schedule in pigeons. Dose-related decreases in response rates were produced by clonidine (0.001-0.1 mg/kg) and morphine (0.3-5.6 mg/kg). Chronic administration of morphine produced (1) tolerance to effects of morphine, as evidenced by a decrease in potency of morphine and (2) sensitivity to opioid antagonists, as evidenced by an increase in potency of naloxone. Dose-effect curves for clonidine were not appreciably altered by chronic morphine administration.