EFFECTS OF MORPHINE ON THE PATHOGENESIS OF MURINE FRIEND RETROVIRUS INFECTION

The immunomodulatory effects of opiates can modify host defenses again st infection. We investigated the mechanisms involved in these effects by studying the influence of morphine on the pathogenesis of murine F riend retrovirus infection. The response to this opiate varied greatly according to the treatment schedule. Daily intraperitoneal administra tion of morphine (50 mg/kg) for 16 to 27 days attenuated pathological manifestations in infected animals without modifying the mortality rat e. The protective effect increased proportionately with the duration o f treatment and depended on the time of treatment initiation relative to inoculation. Naloxone (100 mg/kg/day i.p.) inhibited the morphine-i nduced decrease in both splenomegaly and viral titer. Mifepristone-a g lucocorticoid receptor inhibitor-had no significant effect on the morp hine-induced attenuation of splenomegaly. The influence of the infecti on on acute morphine toxicity was also analyzed using a nonlethal dose in noninfected mice (200 mg/kg). Susceptibility to morphine increased in parallel to the development of the infection, with mortality rates ranging from 20% on day 14 to 90% on day 21. Simultaneous administrat ion of naloxone (20-100 mg/kg) reduced the mortality rate and postpone d death. Administration of mifepristone, terfenadin, phentolamine or p ropranolol did not modify mortality at the doses used. These findings show that the influence of morphine on the development of Friend virus infection in mice depends on the conditions of administration. The tr ansient protective effect seen in certain conditions of administration appears to be due essentially to the direct effects of morphine on it s specific receptors.