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[Effects of morphine on murine infection with Friend retrovirus]
1Département de Pharmacologie clinique, INSERM U. 13, Paris.
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 intra-peritoneal 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 (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 infection on acute morphine toxicity was also analysed, using a non lethal 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 D14 to 90% on D21. 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 used doses. 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 seems 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
Context:
- Opiates, such as morphine, are known to modulate immune responses.
- Understanding these immunomodulatory effects is crucial for managing infections.
- Friend retrovirus infection in mice serves as a model for studying viral pathogenesis and host-pathogen interactions.
Purpose:
- To investigate the mechanisms by which morphine influences the pathogenesis of murine Friend retrovirus infection.
- To determine how different administration schedules of morphine affect the host's response to viral infection.
- To analyze the impact of Friend retrovirus infection on acute morphine toxicity.
Summary:
- Daily intraperitoneal morphine administration (50 mg/kg) for 16-27 days attenuated disease manifestations in Friend retrovirus-infected mice, with protective effects increasing with treatment duration and timing.
- Naloxone, an opioid receptor antagonist, reversed morphine's effects on splenomegaly and viral load, suggesting a role for opioid receptors.
- Conversely, mifepristone, a glucocorticoid receptor inhibitor, did not affect morphine's protective action.
- Susceptibility to acute morphine toxicity increased with the progression of Friend retrovirus infection, indicated by rising mortality rates.
- Naloxone administration reduced morphine-induced mortality in infected mice, while other tested antagonists had no significant effect.
- These findings highlight that morphine's influence on Friend virus infection is schedule-dependent and mediated primarily through direct effects on opioid receptors.
Impact:
- Reveals that morphine's immunomodulatory effects on viral infections are complex and highly dependent on administration parameters.
- Demonstrates the critical role of opioid receptors in mediating both the protective and toxic effects of morphine during viral infection.
- Provides insights into potential therapeutic strategies involving opioids or their antagonists in managing viral pathogenesis and drug toxicity.