Enhanced analgesic potency and reduced tolerance of morphine in 129/SvEv mice: evidence for a deficiency in GM1 ganglioside-regulated excitatory opioid receptor functions

10-fold higher doses in SW mice. Furthermore, cotreatment of 129/SvEv mice with morphine plus a low dose of naltrexone (ca. 0.1 microgram/kg) that markedly enhances and prolongs morphine's antinociceptive effects in SW mice did not enhance, and often attenuated6 h. The marked GM1-induced attenuation of morphine's antinociceptive effects in 129/SvEv mice may be due to conversion of some of the opioid receptors in these mice from an inhibitory Gi/Go-coupled to an excitatory Gs-coupled mode. Exogenous GM1 supplementation can, therefore, reverse the anomalous lack of morphine tolerance displayed by this mouse strain in comparison to SW and other mice. The present study may provide insights into factors that regulate the marked variability in nociceptive sensitivity and opioid tolerance/dependence liability among individual humans.