Abstract

Drug-test interaction as a factor in tolerance development to the analgesic effect of morphine was studied in rats using the hot plate procedure. The rats were randomly divided into five major groups: tested, nontested, tested without agent, ambient temperature tested and ambient temperature tested without agent. Morphine (5 mg/kg s.c.) or saline (2 ml/kg s.c.) was administered once a week. The results dearly demonstrated that the degree of tolerance development was greater when experience was acquired on the plate while under the influence of morphine than when morphine was given in the absence of testing. This effect occurred irrespective of whether the animals received experience on the hot (55°C) plate or the ambient (25°C) plate. Moreover, experience acquired on the plate in the absence of morphine did not alter the responsiveness to a subsequent injection of morphine. These results clearly indicate that a drug-test interaction occurs with morphine and can play a role in the development of tolerance to the analgesic effect of this drug.