Molecular targets of opiate drug abuse in neuroAIDS

Kurt F. Hauser, Nazira El-Hage, Shreya Buch, Joseph R. Berger, William R. Tyor, Avindra Nath, Annadora J. Bruce-Keller, Pamela E. Knapp

Research output: Contribution to journalArticle

Abstract

Opiate drug abuse, through selective actions at μ opioid receptors (MOR), exacerbates the pathogenesis of human immunodeficiency virus-1 (HIV-1) in the CNS by disrupting glial homeostasis, increasing inflammation, and decreasing the threshold for pro-apoptotic events in neurons. Neurons are affected directly and indirectly by opiate-HIV interactions. Although most opiates drugs have some affinity for κ (KOR) and/or δ (DOR) opioid receptors, their neu-rotoxic effects are largely mediated through MOR. Besides direct actions on the neurons themselves, opiates directly affect MOR-expressing astrocytes and microglia. Because of their broad-reaching actions in glia, opiate abuse causes widespread metabolic derangement, inflammation, and the disruption of neuron-glial relationships, which likely contribute to neuronal dysfunction, death, and HIV encephalitis. In addition to direct actions on neural cells, opioids modulate inflammation and disrupt normal intercellular interactions among immu-nocytes (macrophages and lymphocytes), which on balance further promote neuronal dysfunction and death. The neural pathways involved in opiate enhancement of HIV-induced inflammation and cell death, appear to involve MOR activation with downstream effects through PI3-kinase/Akt and/or MAPK signaling, which suggests possible targets for therapeutic intervention in neuroAIDS.

Original languageEnglish (US)
Pages (from-to)63-80
Number of pages18
JournalNeurotoxicity research
Volume8
Issue number1-2
DOIs
StatePublished - Dec 1 2005

Keywords

  • AIDS
  • Astroglia
  • CNS inflammation
  • Chemokines
  • Microglia
  • Neuroimmunology
  • Neurons
  • μ-Opioid receptors

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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  • Cite this

    Hauser, K. F., El-Hage, N., Buch, S., Berger, J. R., Tyor, W. R., Nath, A., Bruce-Keller, A. J., & Knapp, P. E. (2005). Molecular targets of opiate drug abuse in neuroAIDS. Neurotoxicity research, 8(1-2), 63-80. https://doi.org/10.1007/BF03033820