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SIV/Macaque Model of HIV Infection in Cocaine Users: Minimal Effects of Cocaine on Behavior, Virus Replication, and CNS Inflammation

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Abstract

Studies of the effects of drugs of abuse on HIV immune status, disease progression, and neuroAIDS have produced conflicting data and have not definitively shown whether this combination promotes cognitive impairment or disease progression. Using a consistent SIV–macaque model, we investigated the effects of cocaine on behavior, virologic parameters, and CNS inflammation. Macaques received either vehicle or chronic administration of behaviorally active doses of cocaine (1.7 or 3.2 mg/kg/day). Chronic cocaine administration reduced CD8+ T cell counts during acute and late stage infection but had no effect on CD4+ T cell counts. Low-dose cocaine-treated animals had lower CSF vRNA levels late in infection, but cocaine did not alter plasma viral load or vRNA or protein in brain. There were no differences in CSF CCL-2 or interleukin (IL)-6 levels or severity of encephalitis in cocaine-treated as compared to vehicle-treated macaques. There were no differences in brain inflammation or neurodegeneration markers, as determined by interferon (IFN)-β, MxA, CCL2, IL-6, TNFα, IFNγ, and indolamine 2,3-deoxygenase mRNA levels. APP levels also were not altered. The executive function of inhibitory control was not impaired in cocaine-treated or control animals following SIV infection. However, animals receiving 3.2 mg/kg/day cocaine performed more slowly in a bimanual motor test. Thus, chronic administration of cocaine produced only minor changes in behavior, encephalitis severity, CNS inflammation/neurodegeneration, and virus replication in SIV-infected pigtailed macaques, suggesting that cocaine would have only modest effects on the progression of neuroAIDS in HIV-infected individuals.

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Funding authors

MW and MCZ funded this study.

Disclaimers

The authors have no conflict of interests to disclose.

Sources of funding

This study was funded by NIH R01 DA12829, DA05831, and a gift from the Susan R. Scherer Educational Foundation.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, USA

    Michael Weed & Robert D. Hienz

  2. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, 733 N. Broadway, BRB 819, Baltimore, MD, 21205, USA

    Robert J. Adams, Kelly A. Meulendyke, Janice E. Clements, Joseph L. Mankowski & M. Christine Zink

  3. Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, USA

    Michael E. Linde

  4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA

    Janice E. Clements & Joseph L. Mankowski

  5. Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, USA

    Janice E. Clements

  6. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, USA

    Joseph L. Mankowski & M. Christine Zink

  7. Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA

    M. Christine Zink

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  1. Michael Weed
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  2. Robert J. Adams
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  3. Robert D. Hienz
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  4. Kelly A. Meulendyke
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  7. Joseph L. Mankowski
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  8. M. Christine Zink
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Correspondence to M. Christine Zink.

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Weed, M., Adams, R.J., Hienz, R.D. et al. SIV/Macaque Model of HIV Infection in Cocaine Users: Minimal Effects of Cocaine on Behavior, Virus Replication, and CNS Inflammation. J Neuroimmune Pharmacol 7, 401–411 (2012). https://doi.org/10.1007/s11481-011-9281-8

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  • DOI: https://doi.org/10.1007/s11481-011-9281-8

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