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A human xenograft model, in which human peripheral blood mononuclear cells were implanted into severe combined immunodeficiency mice (huPBL-SCID) and infected with a HIV reporter virus, was used to investigate the biological interactions between cocaine and HIV infection. Systemic administration of cocaine (5 mg\/kg\/d) significantly increased the percentage of HIV-infected PBL (two- to threefold) and viral load (100- to 300-fold) in huPBL-SCID mice. Despite the capacity for cocaine to increase corticosterone and adrenocorticotropic hormone levels in control mice, the hypothalamic-pituitary-adrenal axis was suppressed in HIV-infected animals, and corticosterone levels were further decreased when animals were exposed to HIV and cocaine. Activating huPBL in vitro in the presence of 10\u22128 M cocaine increased expression of CC chemokine receptor 5 (CCR5) and CXC chemokine receptor 4 (CXCR4) coreceptors. Expression of CCR5 was also increased at early time-points in the huPBL-SCID model following systemic exposure to cocaine (54.1\u00b19.4% increase over control, P&amp;lt;0.01). This effect preceded the boost in viral infection and waned as HIV infection progressed. Cocaine has been shown to mediate immunosuppressive effects by activating \u03c3-1 receptors in immune cells in vitro and in vivo. Consistent with these reports, a selective \u03c3-1 antagonist, BD1047, blocked the effects of cocaine on HIV replication in the huPBL-SCID mouse. Our results suggest that systemic exposure to cocaine can enhance HIV infection in vivo by activating \u03c3-1 receptors and by modulating the expression of HIV coreceptors.<\/jats:p>","DOI":"10.1189\/jlb.0405219","type":"journal-article","created":{"date-parts":[[2005,10,5]],"date-time":"2005-10-05T03:28:42Z","timestamp":1128482922000},"page":"1198-1203","source":"Crossref","is-referenced-by-count":69,"title":["Cocaine and \u03c3-1 receptors modulate HIV infection, chemokine receptors, and the HPA axis in the huPBL-SCID model"],"prefix":"10.1093","volume":"78","author":[{"given":"Michael D","family":"Roth","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine M","family":"Whittaker","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald P","family":"Tashkin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayle Cocita","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,10,4]]},"reference":[{"key":"2023033022352903800_","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nm0702-673","article-title":"Charting HIV's remarkable voyage through the cell: basic science as a passport to future therapy","volume":"8","author":"Greene","year":"2002","journal-title":"Nat. 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