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Effect of Morphine on the Neuropathogenesis of SIVmac Infection in Indian Rhesus Macaques

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Abstract

Morphine is known to prevent the development of cell-mediated immune (CMI) responses and enhance expression of the CCR5 receptor in monocyte macrophages. We undertook a study to determine the effect of morphine on the neuropathogenesis and immunopathogenesis of simian immunodeficiency virus (SIV) infection in Indian Rhesus Macaques. Hypothetically, the effect of morphine would be to prevent the development of CMI responses to SIV and to enhance the infection in macrophages. Sixteen Rhesus Macaques were divided into three experimental groups: M (morphine only, n = 5), VM (morphine + SIV, n = 6), and V (SIV only, n = 5). Animals in groups M and VM were given 2.5 mg/kg of morphine sulfate, four times daily, for up to 59 weeks. Groups VM and V were inoculated with SIVmacR71/17E 26 weeks after the beginning of morphine administration. Morphine prevented the development of enzyme-linked immunosorbent spot-forming cell CMI responses in contrast to virus control animals, all of which developed CMI. Whereas morphine treatment had no effect on viremia, cerebrospinal fluid viral titers or survival over the time course of the study, the drug was associated with a tendency for greater build-up of virus in the brains of infected animals. Histopathological changes in the brains of animals that developed disease were of a demyelinating type in the VM animals compared to an encephalitic type in the V animals. This difference may have been associated with the immunosuppressive effect of the drug in inhibiting CMI responses.

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Acknowledgments

We thank the following people for their contributions to this work: Sarah Karina, Glaukia Cavalcanti and Kip Fogle for the behavioral training, data analysis, and injections; Heather Hudson and Darcy Griffin for the morphine/saline injections; Dr. Zhuang Li for necropsy services and injections; Dr. David Pinson for the pathological analyses; and Ian Edwards and James Rengel for the technical support. This work was supported by NIH grants DA12827, HD02528, and COBRE P20RR16443.

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Authors and Affiliations

  1. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Mail Stop 3043, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA

    Joanne K. Marcario, Mariam Riazi & Paul D. Cheney

  2. Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA

    Istvan Adany, Himanshu Kenjale, Thomas Yankee & Opendra Narayan

  3. Department of Biostatistics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA

    Olga Nemon & Matthew S. Mayo

  4. Research Design and Analysis Unit, Life Span Institute, Lawrence, KS, 66045, USA

    Kandace Fleming & Janet Marquis

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  1. Joanne K. Marcario
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Correspondence to Paul D. Cheney.

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Marcario, J.K., Riazi, M., Adany, I. et al. Effect of Morphine on the Neuropathogenesis of SIVmac Infection in Indian Rhesus Macaques. J Neuroimmune Pharmacol 3, 12–25 (2008). https://doi.org/10.1007/s11481-007-9085-z

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  • DOI: https://doi.org/10.1007/s11481-007-9085-z

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