title: SIV/macaque model of HIV infection in cocaine users: minimal effects of cocaine on behavior, virus replication, and CNS inflammation.
abstract: Studies of the effects of drugs of abuse on HIV immune status, disease progression, and neuroAIDS have produced conflicting data and have not definitively shown whether this combination promotes cognitive impairment or disease progression. Using a consistent SIV-macaque model, we investigated the effects of cocaine on behavior, virologic parameters, and CNS inflammation. Macaques received either vehicle or chronic administration of behaviorally active doses of cocaine (1.7 or 3.2 mg/kg/day). Chronic cocaine administration reduced CD8+ T cell counts during acute and late stage infection but had no effect on CD4+ T cell counts. Low-dose cocaine-treated animals had lower CSF vRNA levels late in infection, but cocaine did not alter plasma viral load or vRNA or protein in brain. There were no differences in CSF CCL-2 or interleukin (IL)-6 levels or severity of encephalitis in cocaine-treated as compared to vehicle-treated macaques. There were no differences in brain inflammation or neurodegeneration markers, as determined by interferon (IFN)-β, MxA, CCL2, IL-6, TNFα, IFNγ, and indolamine 2,3-deoxygenase mRNA levels. APP levels also were not altered. The executive function of inhibitory control was not impaired in cocaine-treated or control animals following SIV infection. However, animals receiving 3.2 mg/kg/day cocaine performed more slowly in a bimanual motor test. Thus, chronic administration of cocaine produced only minor changes in behavior, encephalitis severity, CNS inflammation/neurodegeneration, and virus replication in SIV-infected pigtailed macaques, suggesting that cocaine would have only modest effects on the progression of neuroAIDS in HIV-infected individuals.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Weed
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
authors.forename: Robert D
authors.initials: RD
authors.lastname: Hienz
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Meulendyke
authors.forename: Michael E
authors.initials: ME
authors.lastname: Linde
authors.forename: Janice E
authors.initials: JE
authors.lastname: Clements
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Mankowski
authors.forename: M Christine
authors.initials: MC
authors.lastname: Zink
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D015658:HIV Infections / Q000150:complications; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008251:Macaca; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology / Q000473:pathology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine