Diazepam attenuates morphine antinociception test-dependently in mice.

The influence of diazepam on the antinociceptive effect of morphine was studied using four different nociceptive tests in mice. In the tail flick test, diazepam induced a dose-dependent reduction of the morphine effect, with an almost total reversed morphine effect following diazepam 2 mg/kg. The effect could not be explained by altered tail skin temperature or pharmacokinetic changes. Diazepam 1 mg/kg and higher induced sedation and significantly impaired the performance in a rotarod test, a dose of 0.5 mg/kg diazepam was therefore used in the other nociceptive tests. This dose of diazepam significantly attenuated the antinociceptive effect of morphine in the constant temperature hot plate test and the tail flick test. In the increasing temperature hot plate test and in the formalin test, no effect of diazepam on the nociceptive effect of morphine was observed. The results indicate that diazepam antagonizes the effect of morphine dependent upon the test employed. No antagonism could be observed in tests with a long-lasting stimulus, and a response integration probably at a rather high level in the CNS. In the two tests showing antagonism, the stimulus is more short-lasting, and at least for the tail flick test, the integration takes place at a lower level in the CNS.