Effect of thyrotropin releasing hormone on the development of tolerance to the analgesic and hyperthermic actions of morphine in the rat.

The effect of thyrotropin releasing hormone (TRH) on the development of tolerance to the analgesic and hyperthermic actions of morphine was determined in male Sprague-Dawley rats. The tolerance to morphine was induced by subcutaneous implantation of 6 morphine pellets, each containing 75 mg of morphine free base. Rats serving as controls were implanted with 6 placebo pellets. Subcutaneous injections of TRH (1, 3 or 10 mg/kg) twice a day for 7 days inhibited the development of tolerance to the analgesic, but not to the hyperthermic action of morphine. Doses lower than 1 mg/kg or greater than 10 mg/kg administered twice a day for 7 days did not modify tolerance development. The inability of higher doses of TRH to inhibit tolerance to morphine may be related to rapid down-regulation of TRH receptors. The results suggest that in appropriate doses, TRH can selectively inhibit the development of tolerance to the analgesic action of morphine.