The up-and-down method substantially reduces the number of animals required to determine antinociceptive ED50 values

As a consequence of an awareness of animal welfare concerns, one of the goals in biomedical research is to reduce, whenever possible, the number of laboratory animals used for experimentation. The up-and-down method is a procedure that has been confirmed to reduce the number of animals needed to determine LD50 values without compromising reliability. The purpose of the present study was to evaluate whether the up-and-down method could be applied to reduce the number of animals required to obtain the ED50 values of various antinociceptive agents. The ED50 values of morphine, heroin, fentanyl, codeine, meperidine, delta9-THC, CP 55,940, nicotine, and epibatidine for mice in the tail-flick test did not differ between the up-and-down method and a traditional dose-response procedure. Whereas a mean of 28 mice/drug were used in the dose-response procedure, only eight mice/drug were used in the up-and-down method. Moreover, the ED50 values calculated by both methods were highly correlated with each other (r = 0.99). Similarly, intracerebroventricular administration of either delta9-THC or CP 55,940 to rats resulted in nearly identical ED50 values for both methods. These results support the use of the up-and-down method as an effective procedure to reduce substantially the number of animals needed to determine ED50 values of a variety of antinociceptive drugs.