Cocaine Enhances Human Immunodeficiency Virus Replication in a Model of Severe Combined Immunodeficient Mice Implanted with Human Peripheral Blood Leukocytes

Roth, Michael D.; Tashkin, Donald P.; Choi, Rachel; Jamieson, Beth D.; Zack, Jerome A.; Baldwin, Gayle Cocita

doi:10.1086/339012

Cited by 99 publications

(86 citation statements)

References 14 publications

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“…For example, in vitro experiments suggest that HIV replication is maximally stimulated by 24 hours of exposure to nanomolar cocaine concentrations and normalizes to control levels at higher concentrations (Peterson et al, 1991;Peterson et al, 1992). A similar increased HIV replication, as well as altered immune cell populations in peripheral tissues, was reported following a 5 mg/kg dose of cocaine in SCID mice (Roth et al, 2002;Roth et al, 2005). Although these reports suggest that cocaine doses lower than the 20 mg/kg dose used in the present experiment might enhance HIVE parameters, whether these lower doses are relevant to the drug's rewarding/reinforcing effects in SCID mice is unknown.…”

Section: Discussionsupporting

confidence: 79%

Chronic cocaine exposure in the SCID mouse model of HIV encephalitis

2007

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Clinical and preclinical evidence suggests that cocaine exposure hastens progression of the HIV disease process. An established active, euphoric dose of cocaine (20 mg/kg) was administered to SCID mice according to a regimen consistent with exposure to the drug by cocaine-abusing HIVinfected patients to determine the effects of cocaine on four previously established pathological characteristics of HIV encephalitis: cognitive deficits, fatigue, astrogliosis, and microgliosis. Mice were intracranially inoculated with either HIV-infected, or uninfected macrophages and then injected with either cocaine or saline in a 2(Infection) × 2(Cocaine) factorial design. Cognition was assessed by acquisition and retention of a spatially cued learning task. Fatigue was assessed by monitoring motor activity following a 2 minute forced swim. Mice were then sacrificed to determine the extent of astrogliosis and microgliosis in the four groups. Results indicated that in comparison to uninfected controls, HIV positive mice had increased astrogliosis and microgliosis, cognitive deficits, and recovered more slowly from fatigue. However, despite evidence that the cocaine exposure regimen activated the central nervous system and had long-term CNS effects, the drug did not alter the behavioral or the neuropathological deficits noted in HIV-infected SCID mice.

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Section: Discussionsupporting

confidence: 79%

Chronic cocaine exposure in the SCID mouse model of HIV encephalitis

2007

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“…Methamphetamine itself also increased replication of feline immunodeficiency virus in cultured feline astrocytes (29). Likewise, cocaine, which was abused occasionally by the majority of the HIV-positive subjects with a history of chronic methamphetamine use in the current study, might further enhance HIV replication (30), although cocaine's direct effect on N-acetylaspartate would be minimal (31). Thus, the intermittently increased viral burden in the combined condition might exacerbate brain injury.…”

Section: Discussionmentioning

confidence: 73%

Additive Effects of HIV and Chronic Methamphetamine Use on Brain Metabolite Abnormalities

Chang

Ernst²,

Speck³

et al. 2005

AJP

162

120

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Objective-Proton magnetic resonance spectroscopy ( 1 H-MRS) showed decreased neuronal marker N-acetylaspartate and increased glial marker myo-inositol in subjects with chronic methamphetamine use and in subjects infected with HIV. The authors sought to determine whether HIV and a history of chronic methamphetamine use might have additive or interactive effects on brain metabolite abnormalities.Method-1 H-MRS was performed in 68 HIV-positive subjects (24 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 2,167 g [SD=2,788] and last use a mean of 4.9 months earlier [SD=6.0]; 44 with no history of drug abuse) and 75 HIV-negative subjects (36 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 8,241 g [SD=16,850] and last use a mean of 6.3 months earlier [SD=7.8]; 39 with no history of drug abuse). Concentrations of N-acetylaspartate, creatine, choline, and myo-inositol were measured in the frontal cortex, frontal white matter, and basal ganglia.Results-HIV-negative subjects with a history of chronic methamphetamine use showed lower concentrations of the neuronal marker N-acetylaspartate in the frontal white matter and basal ganglia and higher concentrations of choline compounds and the glial marker myo-inositol in the frontal cortex, relative to subjects with no history of drug abuse. HIV-positive status was associated with lower concentrations of N-acetylaspartate and creatine in the frontal cortex and higher concentrations of myo-inositol in the white matter, compared with HIV-negative status.Compared to the mean concentrations of metabolites in HIV-negative subjects with no history of drug abuse, the mean concentrations in subjects with HIV and chronic methamphetamine use showed additive effects on N-acetylaspartate in all three regions (−9% in the basal ganglia, −7% in the frontal white matter, and −6% in the frontal gray matter), on creatine in the basal ganglia (−7%), and on myo-inositol in the frontal white matter (+11%).Conclusions-The combined effects of HIV and chronic methamphetamine use were consistent with an additive model, suggesting additional neuronal injury and glial activation due to the comorbid conditions.Address correspondence and reprint requests to Dr. Chang, Department of Medicine, John A. Burns School of Medicine, University of Hawaii, 1356 Lusitana St., 7th Floor, Honolulu, HI 96813; LChang@hawaii.edu. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptMethamphetamine, a psychostimulant with reinforcing effects similar to those of cocaine (1), has re-emerged as a major drug of abuse worldwide and is commonly used among HIVinfected individuals. In Thailand, both inhalation and injection of methamphetamine are associated with higher risk for HIV infection (2). Similarly, studies and large surveys in the United States (California and New York) consistently found that even noninjection methamphetamine use contributes to higher rates of unprotected sexual activity in both men and wo...

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“…Cocaine increases HIV infection of human PBMCs in vitro (12,177). Roth et al, using a model of human PBMCs implanted into severe combined immunodeficient (SCID) mice, demonstrated that cocaine treatments resulted in increased numbers of HIV-infected PBMCs and viral load, as well as a decreased CD4/ CD8 ratio (192). These immunomodulations may be through receptors located in the periphery, as was demonstrated with cocaine-induced suppression of mitogen-stimulated lymphoproliferation (171).…”

Section: Cocaine and Infectionsmentioning

confidence: 99%

Microbial Infections, Immunomodulation, and Drugs of Abuse

2003

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The use of recreational drugs of abuse has generated serious health concerns. There is a long-recognized relationship between addictive drugs and increased levels of infections. Studies of the mechanisms of actions of these drugs became more urgent with the advent of AIDS and its correlation with abused substances. The nature and mechanisms of immunomodulation by marijuana, opiates, cocaine, nicotine, and alcohol are described in this review. Recent studies of the effects of opiates or marijuana on the immune system have demonstrated that they are receptor mediated, occurring both directly via specific receptors on immune cells and indirectly through similar receptors on cells of the nervous system. Findings are also discussed that demonstrate that cocaine and nicotine have similar immunomodulatory effects, which are also apparently receptor mediated. Finally, the nature and mechanisms of immunomodulation by alcohol are described. Although no specific alcohol receptors have been identified, it is widely recognized that alcohol enhances susceptibility to opportunistic microbes. The review covers recent studies of the effects of these drugs on immunity and on increased susceptibility to infectious diseases, including AIDS

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Cocaine Enhances Human Immunodeficiency Virus Replication in a Model of Severe Combined Immunodeficient Mice Implanted with Human Peripheral Blood Leukocytes

Cited by 99 publications

References 14 publications

Chronic cocaine exposure in the SCID mouse model of HIV encephalitis

Chronic cocaine exposure in the SCID mouse model of HIV encephalitis

Additive Effects of HIV and Chronic Methamphetamine Use on Brain Metabolite Abnormalities

Microbial Infections, Immunomodulation, and Drugs of Abuse

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