The brain is a target organ for recreational drugs and HIV-1. Epidemiological 
data demonstrate that opioid abuse is a risk factor for HIV-1 infection and 
progression to AIDS. Chemokines and their receptors have been implicated in the 
neuropathogenesis of HIV-1 infections. However, little is known about the 
effects of opioids on the expression of chemokines and their receptors (the 
latter also are HIV-1 coreceptors) by cells of the CNS. Herein we describe the 
effects of morphine on gene expression of the alpha- and beta-chemokines and 
their receptors by the astrocytoma cell line U87 and by primary normal human 
astrocyte (NHA) cultures. U87 cells treated with morphine showed significant 
down-regulation of IL-8 gene expression, whereas expression of the IL-8 receptor 
CXCR2 was reciprocally up-regulated as detected by RT-PCR. Treatment of NHAs 
with morphine suppressed IL-8 and macrophage-inflammatory protein-1beta gene 
expression, whereas expression of their receptor genes, CCR3 and CCR5, was 
simultaneously enhanced. These morphine-induced effects on U87 and NHA cells 
were reversed by the opioid mu receptor antagonist beta-funaltrexamine. Morphine 
also enhanced the constitutive expression of the opioid mu receptor on 
astroglial cells. Our results support the hypothesis that opioids play a 
significant role in the susceptibility of the CNS to HIV-1 infection and 
subsequent encephalopathy by inhibiting local production of HIV-1-protective 
chemokines (IL-8 and macrophage-inflammatory protein-1beta) and enhancing 
expression of HIV-1 entry coreceptor genes (CCR3, CCR5, and CXCR2) within the 
CNS. These effects of opioids appear to be mediated through the opioid mu 
receptor that we demonstrated on astroglial cells.