EFFECTS OF MORPHINE ON THE PATHOGENESIS O F 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 intra-peritoneal administr ation of morphine (50 mg/kg) for 16 to 27 days attenuated pathological manifestations in infected animals without modifying the mortality ra te. The protective effect increased proportionately with the duration of treatment, and depended on the time of treatment initiation relativ e to inoculation. Naloxone (10 mg/kg/day i.p.) inhibited the morphine- induced decrease in both splenomegaly and viral titer. Mifepristone - a glucocorticoid receptor inhibitor - had no significant effect on the morphine-induced attenuation of splenomegaly. The influence of the in fection on acute morphine toxicity was also analysed, using a non leth al dose in noninfected mice (200 mg/kg). Susceptibility to morphine in creased in parallel to the development of the infection, with mortalit y rates ranging from 20 % on D14 to 90 % on D21. Simultaneous administ ration of naloxone (20-100 mg/kg) reduced the mortality rate and postp oned death. Administration of mifepristone, terfenadin, phentolamine o r propranolol did not modify mortality at the used doses. These findin gs show that the influence of morphine on the development of Friend vi rus infection in mice depends on the conditions of administration. The transient protective effect seen in certain conditions of administrat ion seems to be due essentially to the direct effects of morphine on i ts specific receptors.