A revised rotarod procedure for measuring the effect of antinociceptive drugs on motor function in the rat.

Tests of putative antinociceptive agents that rely on a motor response of an experimental animal to a noxious stimulus will give false positive results, and may be unethical, if the agent compromises motor function. We report a procedure for measuring potential effects of antinociceptive agents on motor function in the trained rat, using an 80 mm diameter rotarod. Rats were selected for ability to exercise on the rotarod and trained to increasing speeds. In test trials, we measured the time that trained rats could stay on the rod, rotating at 25 rpm, with a cut off at 60 min. Morphine administration decreased rotarod performance significantly at doses of 5.0 mg/kg (P less than 0.05, n = 10) and 7.5 mg/kg (P less than 0.005, n = 10). We also assessed the response to a noxious thermal stimulus by measuring tail flick latency following tail immersion in water at 49 degrees C. A significant dose-dependent increase in tail flick latency was found for dosages of morphine between 2.5 mg/kg and 7.5 mg/kg (P less than 0.005, n = 10). Our rotarod procedure, which incorporates selection, training, and a 60 min trial, provides a sensitive and consistent means of assessing motor function. Our results, implying that morphine indeed compromises motor function in rats at doses at which it is antinociceptive, confirm the necessity for investigating the motor effects of any putative antinociceptive agent.