Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND

J Neuroimmune Pharmacol. 2013 Jun;8(3):621-42. doi: 10.1007/s11481-013-9443-y. Epub 2013 Mar 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • AIDS Dementia Complex / chemically induced
  • AIDS Dementia Complex / immunology
  • AIDS Dementia Complex / metabolism*
  • Animals
  • Central Nervous System / drug effects
  • Central Nervous System / immunology
  • Central Nervous System / metabolism
  • Dopamine / metabolism*
  • Dopamine Agents / pharmacology
  • Dopamine Agents / toxicity
  • HIV Infections / immunology
  • HIV Infections / metabolism*
  • Humans
  • Illicit Drugs / pharmacology
  • Illicit Drugs / toxicity
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Dopamine Agents
  • Illicit Drugs
  • Dopamine