Differential antinociception by morphine and methadone in two sub-strains of Sprague-Dawley rats and its potentiation by dextromethorphan.

The antinociceptive effect of morphine and methadone was tested in two substrains of Sprague-Dawley (SD) rats, from B&K Universal, Sweden (BK) and Mollegård, Denmark (DK). In both sub-strains of SD rats subcutaneous morphine or methadone produced dose-dependent antinociception on the hot plate test. However, the effect of the opioids was less in DK-SD than BK-SD rats, particularly for morphine as it failed to produce maximal antinociception even at high doses. Dextromethorphan, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, potentiated the antinociceptive effect of morphine and methadone in the DK-SD rats. The potentiation of morphine by dextromethorphan was significantly greater than its effect on methadone at equipotent doses. The results showed that there is a sub-strain difference for SD rats in the response to the antinociceptive effect of opioids, which may be due to greater NMDA receptor activity in DK-SD than in BK-SD rats. The higher efficacy of methadone may be derived from its proposed NMDA receptor blocking property and/or high intrinsic activity.