Molecular targets of opiate drug abuse in neuroAIDS Article

cited authors

  • Hauser, KF; El-Hage, N; Buch, S; Berger, JR; Tyor, WR; Nath, A; Bruce-Keller, AJ; Knapp, PE

fiu authors

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. © Springer 2005.

publication date

  • December 1, 2005

Digital Object Identifier (DOI)

start page

  • 63

end page

  • 80

volume

  • 8

issue

  • 1-2