HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens.
BACKGROUND Recently, the NIH called for additional research on the topic of viral and host factors contributing to impaired cognitive and neural function in HIV/AIDS patients and their response to antiretroviral treatment. This investigation responds to that call by examining a host factor, a family history of substance dependence, often overlooked in cognitive and neuroimaging studies of HIV/AIDS. METHODS We categorized 146 HIV-1 seropositive patients receiving antiretroviral treatment (ART) and 92 seronegative volunteers by the presence or absence of alcohol, cocaine, or heroin dependence affecting a biological parent. Seropositive patients were further categorized by the estimated ability of their individual ART regimens to penetrate the CNS. The indicator of brain function was a 3-7Hz oscillatory electroencephalographic response (theta ERO) evoked by target stimuli presented during a simple selective attention task. RESULTS The analysis revealed that the presence of a family history of substance dependence obscured the reduction in frontal theta ERO power accompanying the presence of HIV-1 as well as the improvement in frontal theta ERO power accompanying treatment with ART agents estimated to have greater (n=41) versus lesser (n=105) CNS penetrance. Secondary analyses employing sLORETA source localization techniques revealed that the source of the theta ERO response was similarly reduced by the presence of either HIV-1 or a family history of substance dependence. CONCLUSIONS We conclude that a family history of substance dependence complicates and obscures the subtle neurophysiological changes which typically accompany HIV/AIDS and ART. Studies of new therapeutic agents for HIV-1-associated cognitive and neurophysiological impairments must consider this complication and exclude or control it.