Ml. Veyries et al., EFFECTS OF MORPHINE ON THE PATHOGENESIS OF MURINE FRIEND RETROVIRUS INFECTION, The Journal of pharmacology and experimental therapeutics, 272(2), 1995, pp. 498-504
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.