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Drug Induced Increases in CNS Dopamine Alter Monocyte, Macrophage and T Cell Functions: Implications for HAND

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Abstract

Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70 % of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers.

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Acknowledgments

We thank all of the members of Dr. Joan W. Berman’s laboratory at Einstein, especially Lillie Lopez and Dionna Williams, for important discussions, and Dr. Jonathan A. Javitch, at Columbia University Medical Center, for assistance with Table 1. We also thank Dr. Brad Poulos and the Fetal Tissue Repository, the Einstein Flow Cytometry Facility and the Einstein Center For AIDS Research (AI-051519) for their assistance. These studies were funded by grants from the National Institutes of Drug Abuse, DA029476 (PJG) and DA025567 (JSC, TMC and JWB), and the National Institutes of Mental Health, MH090958 (TMC and JWB) and MH075679 (TMC and JWB).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA

    Peter J. Gaskill, Tina M. Calderon, Jacqueline S. Coley & Joan W. Berman

  2. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA

    Joan W. Berman

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  1. Peter J. Gaskill
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  2. Tina M. Calderon
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Correspondence to Joan W. Berman.

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Peter J. Gaskill and Tina M. Calderon contributed equally to this work.

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Gaskill, P.J., Calderon, T.M., Coley, J.S. et al. Drug Induced Increases in CNS Dopamine Alter Monocyte, Macrophage and T Cell Functions: Implications for HAND. J Neuroimmune Pharmacol 8, 621–642 (2013). https://doi.org/10.1007/s11481-013-9443-y

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