Oxytocin diminishes heroin tolerance in mice

Tolerance was induced in mice to the antinociceptive effect of heroin by repeated subcutaneous injections of this narcotic analgesic for 3 days. Pretreatment of mice with daily doses of oxytocin (2-200 micrograms/kg body wt.) resulted in an attenuation of heroin tolerance. A single oxytocin injection prior to the first challenge with heroin was as active in attenuating heroin tolerance as daily treatments with the neuropeptide. A single injection of oxytocin prior to the least heroin challenge also attenuated the expression of tolerance. The neuropeptide failed to modify the acute antinociceptive effect of heroin. It is concluded, therefore, that oxytocin interferes with mechanisms involved in the development and expression of tolerance to heroin.