ORAL-ADMINISTRATION OF DEXTROMETHORPHAN PREVENTS THE DEVELOPMENT OF MORPHINE-TOLERANCE AND DEPENDENCE IN RATS

Combined oral administration of morphine sulfate (MS) and the over-the -counter antitussive drug and N-methyl-D-aspartate receptor antagonist dextromethorphan (DM) prevented the development of tolerance to the a ntinociceptive effects of MS (15, 24, or 32 mg/kg) in rats. This combi ned oral treatment regimen also attenuated signs of naloxone-precipita ted physical dependence on morphine in the same rats. A wide range of ratios of MS to DM (2:1, 1:1, and 1:2) were effective for preventing t he development of morphine tolerance and dependence. In addition, we p rovide evidence that under certain circumstances DM increases the acut e antinociceptive effects of MS. All of these results indicate that or al treatment that combines DM with opiate analgesics may be a powerful approach for simultaneously preventing opiate tolerance and dependenc e and enhancing analgesia in humans.