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Despite this, the mechanisms by which opiates increase the neuropathogenesis of HIV are uncertain. In the present study, we describe the effect of morphine and the HIV\u20101 protein toxin Tat<jats:sub>1\u201072<\/jats:sub> on astroglial function in cultures derived from ICR mice. Astroglia maintain the blood\u2010brain barrier and influence inflammatory signaling in the CNS. Astrocytes can express \u03bc\u2010opioid receptors, and are likely targets for abused opiates, which preferentially activate \u03bc\u2010opioid receptors. While Tat alone disrupts astrocyte function, when combined with morphine, Tat causes synergistic increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Moreover, astrocyte cultures treated with morphine and Tat showed exaggerated increases in chemokine release, including monocyte chemoattractant protein\u20101 (MCP\u20101) and regulated on activation, normal T cell expressed and secreted (RANTES), as well as interleukin\u20106 (IL\u20106). Morphine\u2010Tat interactions were prevented by the \u03bc\u2010opioid receptor antagonist \u03b2\u2010funaltrexamine, or by immunoneutralizing Tat<jats:sub>1\u201072<\/jats:sub> or substituting a nontoxic, deletion mutant (Tat<jats:sub>\u039431\u201061<\/jats:sub>). Our findings suggest that opiates may increase the vulnerability of the CNS to viral entry (via recruitment of monocytes\/macrophages) and ensuing HIV encephalitis by synergistically increasing MCP\u20101 and RANTES release by astrocytes. The results further suggest that astrocytes are key intermediaries in opiate\u2010HIV interactions and disruptions in astroglial function and inflammatory signaling may contribute to an accelerated neuropathogenesis in HIV\u2010infected individuals who abuse opiates. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20148","type":"journal-article","created":{"date-parts":[[2005,1,3]],"date-time":"2005-01-03T18:17:09Z","timestamp":1104776229000},"page":"91-106","source":"Crossref","is-referenced-by-count":191,"title":["Synergistic increases in intracellular Ca<sup>2+<\/sup>, and the release of MCP\u20101, RANTES, and IL\u20106 by astrocytes treated with opiates and HIV\u20101 Tat"],"prefix":"10.1002","volume":"50","author":[{"given":"Nazira","family":"El\u2010Hage","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie 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