The effect of U-50,488H, a kappa-opiate receptor agonist on tolerance to the analgesic and hyperthermic effects of morphine in the rat.

1. The effect of intraperitoneal injections of U-50,488H, a kappa-opiate receptor agonist, on the development of tolerance to the analgesic and hyperthermic effects of morphine was determined in male Sprague-Dawley rats. 2. Tolerance was induced by implantation of four morphine pellets during a 3-day period (4/3 schedule) or six morphine pellets during a 7-day period (6/7 schedule). 3. Administration of U-50,488H (25 mg/kg, twice a day for 3 days in 4/3 schedule) or (5, 10 and 20 mg/kg twice a day for 7 days in 6/7 schedule) did not affect the development of tolerance to the pharmacological actions of morphine. 4. It is concluded that activation of kappa-opiate receptors does not modify the development of tolerance to morphine in the rat.