Fig. 2.

Summary of key intercellular events by which opiates may exacerbate the pathogenesis of HIV in the CNS. Opiates exaggerate the neuropathogenesis of HIV through direct actions on opioid receptor-expressing neurons, astrocytes, and microglia (blue arrowheads in “HIV-Infected + Opiate Abuse”). Note that opiates amplify the toxic actions of HIV, but do not result in additional insults. Opiates affect each cell type differently, which collectively results in disruptions in neuronal dysfunction and death. Leukocytes, within CNS blood vessels (Peripheral Leukocytes), including monocytes/macrophages and T-lymphocytes, can express opioid receptors and respond directly to opiates (arrows indicate intercellular signaling events; lines ending in a “T” indicate quiescent signaling; pathways & abbreviations are noted in the text).