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Effects of morphine on the pathogenesis of murine Friend retrovirus infection
M L Veyries1, M Sinet, B Desforges
1Département de Pharmacologie Clinique, Hôpital Claude Bernard, Institut National de la Santé et de la Recherche Médicale U13, Paris, France.
Abstract:
The immunomodulatory effects of opiates can modify host defenses against infection. We investigated the mechanisms involved in these effects by studying the influence of morphine on the pathogenesis of murine Friend retrovirus infection. The response to this opiate varied greatly according to the treatment schedule. Daily intraperitoneal administration of morphine (50 mg/kg) for 16 to 27 days attenuated pathological manifestations in infected animals without modifying the mortality rate. The protective effect increased proportionately with the duration of treatment and depended on the time of treatment initiation relative to inoculation. Naloxone (100 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 infection 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 administration of naloxone (20-100 mg/kg) reduced the mortality rate and postponed death. Administration of mifepristone, terfenadin, phentolamine or propranolol 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 transient protective effect seen in certain conditions of administration appears to be due essentially to the direct effects of morphine on its specific receptors.
Insights
Morphine administration can alter host defenses, impacting Friend retrovirus infection in mice. The drug
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Opiates, like morphine, are known to modulate host immune responses.
- Understanding these immunomodulatory effects is crucial for managing infectious diseases.
Purpose of the Study:
- To investigate the mechanisms by which morphine influences the pathogenesis of Friend retrovirus infection in mice.
- To determine how different morphine treatment schedules affect the host's response to viral infection and drug toxicity.
Main Methods:
- Mice were infected with Friend retrovirus and treated with varying schedules of morphine (50 mg/kg).
- Naloxone, mifepristone, terfenadine, phentolamine, and propranolol were administered to assess the roles of opioid and other receptors.
- Viral titers, splenomegaly, and mortality rates were monitored to evaluate treatment effects.
Main Results:
- Daily morphine administration attenuated splenomegaly and reduced viral titers, with effects dependent on treatment duration and timing.
- Naloxone reversed the protective effects of morphine, suggesting opioid receptor involvement.
- Mice infected with Friend retrovirus showed increased susceptibility to morphine toxicity, which was partially mitigated by naloxone.
Conclusions:
- Morphine's influence on Friend virus infection is schedule-dependent, with transient protective effects observed under specific conditions.
- These protective effects appear to be mediated by direct interactions of morphine with its specific receptors.
- The study highlights the complex interplay between opioid administration, viral pathogenesis, and host immune responses.