Chronic cocaine exposure in the SCID mouse model of HIV encephalitis

Abstract

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.

SIV/Macaque Model of HIV Infection in Cocaine Users: Minimal Effects of Cocaine on Behavior, Virus Replication, and CNS Inflammation

“…The results of the present study are also consistent with studies in the SCID-HIV model of AIDS, which indicated that cocaine did not exacerbate known motor and cognitive impairments caused by HIV (Griffin et al 2007). As reported previously, there was a significant correlation between impairment on the BMS task and APP accumulation in the corpus collosum (Weed et al 2003).…”

Highly active antiretroviral therapy of cognitive dysfunction and neuronal abnormalities in SCID mice with HIV encephalitis

“…The brains of these SCID mice inoculated intracerebrally with HIV-infected human monocytes characteristically have HIV-infected human mononuclear phagocytes, multinucleated giant cells, increased human cytokine expression, and increased levels of astrocytes and microglia, most notably, astrogliosis (Tyor 1993, Persidsky 1996, Griffin 2004, Cook 2005, Griffin 2007. Furthermore, these infected SCID mice with characteristic HIVE neuropathology have cognitive deficits (Avgeropoulos 1998, Griffin 2004, Griffin 2007. The pathological and cognitive deficits in HIVE SCID mice are similar to those seen in humans with HAD.…”

“…A SCID mouse model of HIVE was developed to help further elucidate the pathogenesis of HAD (Tyor 1993, Persidsky 1996, Avgeropoulos 1998, Griffin 2004, Cook 2005. The brains of these SCID mice inoculated intracerebrally with HIV-infected human monocytes characteristically have HIV-infected human mononuclear phagocytes, multinucleated giant cells, increased human cytokine expression, and increased levels of astrocytes and microglia, most notably, astrogliosis (Tyor 1993, Persidsky 1996, Griffin 2004, Cook 2005, Griffin 2007. Furthermore, these infected SCID mice with characteristic HIVE neuropathology have cognitive deficits (Avgeropoulos 1998, Griffin 2004, Griffin 2007.…”

Cocaine Potentiates Cathepsin B Secretion and Neuronal Apoptosis from HIV-Infected Macrophages

“…Proteomics analyses have revealed the enhancement of HIV-replication in normal human astrocytes after exposure to cocaine (Reynolds et al 2006). The interaction of HIV-1 with cocaine has also been evaluated using an in vivo mouse model with severe combined immunodeficiency which revealed that cocaine enhances the HIV-replication (Roth et al 2002; Griffin et al 2007). …”