Neurotoxicity Research

, Volume 8, Issue 1–2, pp 63–80 | Cite as

Molecular targets of opiate drug abuse in neuro AIDS

  • Kurt F. Hauser
  • Nazira El-Hage
  • Shreya Buch
  • Joseph R. Berger
  • William R. Tyor
  • Avindra Nath
  • Annadora J. Bruce-Keller
  • Pamela E. Knapp
Part I HIV-1 Asociated Dementia (HAD)


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.


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



adenylyl cyclase


alpha chemokine receptor


apoptosis protease activity factor


beta chemokine ligand


beta chemokine receptor




caspase activated DNAse


c-jun-N-terminal kinase


cAMP response element binding protein


δ-opioid receptor


excitatory amino acid transporter-2


extracellular-regulated kinase


G-protein coupled receptor


glycogen synthase kinase 3β


forkhead transcription factor


hepatitis C virus


HIV associated dementia


human immunodeficiency virus


human immunodeficiency virus encephalitis


IκB kinase


inositol trisphosphate






intracellular Ca2+


κ-opioid receptor


low-density lipoprotein; receptor-related protein

(mannose receptor)

mannose R


microtubule associated proteins


mitogen-activated protein kinase

(MCP-1 or CCL2)

monocyte chemoattractant protein-1


μ-opioid receptor


nitric oxide




nuclear factor κB


oligodendroctye-type-2 astrocyte progenitor cell

(PI3- kinase or PI3K)

phosphatidylinositol 3-kinase


phosphoinositide-dependent kinase 1


phospholi-pase C-γ


phosphatase and tensin homolog deleted on chromosome 10


pleckstrin homology


protein kinase A

(PKB, also known as Akt)

protein kinase B


protein kinase C


regulated on activation, normal T cell expressed and secreted


reactive oxygen species


transactivator of transcription


tumor necrosis factor-α


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Copyright information

© Springer 2005

Authors and Affiliations

  • Kurt F. Hauser
    • 1
    • 2
    • 5
  • Nazira El-Hage
    • 1
    • 5
  • Shreya Buch
    • 1
    • 5
  • Joseph R. Berger
    • 3
    • 5
  • William R. Tyor
    • 4
    • 5
  • Avindra Nath
    • 3
    • 5
  • Annadora J. Bruce-Keller
    • 1
    • 2
    • 5
  • Pamela E. Knapp
    • 1
    • 2
    • 5
  1. 1.Department of Anatomy and NeurobiologyUniversity of Kentucky Medical CenterLexingtonUSA
  2. 2.Department of Spinal Cord & Brain Injury Research Center (SCoBIRC)University of Kentucky Medical CenterLexingtonUSA
  3. 3.Department of Department of NeurologyUniversity of Kentucky Medical CenterLexingtonUSA
  4. 4.Department of NeurosciencesMedical University of South CarolinaCharlestonUSA
  5. 5.Department of NeurologyJohns Hopkins UniversityBaltimoreUSA

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