Morphine-potentiated cognitive deficits correlate to suppressed hippocampal iNOS RNA expression and an absent type 1

Virginia D McLane1, Saurabh Kumar2, Reno Leeming3

  • 1University of Maine, Graduate School of Biomedical Science and Engineering, Orono, ME 04669, USA; University of New England, College of Osteopathic Medicine, Biddeford, ME 04005, USA.

Insights

Opioid use worsens cognitive decline in HIV/AIDS. Morphine impacted brain inflammation and cognitive function in mice with murine AIDS (MAIDS), suggesting varied type 1 interferon responses contribute to regional brain effects.

Area of Science:

  • Neuroimmunology
  • Infectious Diseases
  • Neurovirology

Background:

  • Human Immunodeficiency Virus (HIV) infection is associated with accelerated neurocognitive impairment.
  • Opioid use is common in HIV patients and may exacerbate neurological complications.
  • The interplay between opioid use, HIV-associated neuroinflammation, and cognitive function requires further investigation.

Purpose of the Study:

  • To investigate the effects of chronic morphine treatment on cognition, cytokine production, and type 1 interferon (IFN) expression in the central nervous system (CNS) of mice infected with LP-BM5/murine AIDS (MAIDS).
  • To determine the relationship between morphine-induced changes, viral load, and neuroinflammation in specific brain regions (hippocampus and striatum).

Main Methods:

  • Mice were infected with LP-BM5 to induce MAIDS.
  • Chronic morphine treatment was administered to infected and uninfected mice.
  • Cognitive performance, cytokine expression (CCL5, iNOS), type 1 IFN (IFN-α) RNA expression, and viral load in the CNS were assessed.

Main Results:

  • Morphine treatment reduced pro-inflammatory factors (CCL5, iNOS) and impaired cognitive performance in LP-BM5-infected mice.
  • These cognitive deficits correlated with increased hippocampal viral load and a blunted type 1 IFN response.
  • In the striatum, morphine reduced viral load but increased IFN-α RNA expression, indicating region-specific effects.

Conclusions:

  • Chronic morphine treatment differentially affects neuroinflammation and viral load in the hippocampus and striatum of MAIDS mice.
  • Regionally distinct type 1 interferon responses may underlie differential outcomes in the CNS during combined HIV infection and opioid exposure.
  • These findings highlight the complex interactions between opioids, viral infection, and the CNS immune response.

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