DEVELOPMENT OF TOLERANCE TO ANTINOCICEPTIVE EFFECTS OF AN INTRATHECALMORPHINE CLONIDINE COMBINATION IN RATS/

Previous animal studies have shown the antinociceptive effects of intr athecal clonidine and intrathecal morphine to be synergistic. This stu dy investigated the intrathecal administration of multiple doses of th is drug combination to examine the rate of development of tolerance an d to determine whether there was any toxic effect on the spinal cord. Rats with indwelling intrathecal catheters were given saline, morphine (2.5-7.5 mu g), clonidine (17.5 mu g), or clonidine(17.5 mu g) plus m orphine(1 mu g) intrathecally twice daily for 4 1/2 days (total of 9 d oses). Hot plate and tail flick tests were conducted after the first, fifth and ninth doses. After the ninth dose animals were killed and th eir spinal cords were removed for histological examination. Tolerance developed to the antinociceptive effects of the drug combination, but at a slower rate than to morphine alone. No evidence of toxicity or in jury to the spinal cord was observed other than changes which could be ascribed to the presence of the catheter.