ALCOHOL AND HIV INFECTION: ADDITIVE NEUROPHYSCHOLOGICAL EFFECTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alcohol and Human Immunodeficiency Virus (HIV) infection have been shown to produce similar neuropathological profiles, including loss of neurons in the frontal cortex. Additionally, 50-75% of HIV-infected adults are diagnosed with neurological problems, and 20% develop Acquired Immunodeficiency Syndrome (AIDS) dementia. There is also experimental evidence indicating that chronic alcohol consumption potentiates AIDS-related neuropathy. For example, HIV-positive patients who are long-term abusers of alcohol generally have greater neurologic deficits, and chronic alcohol abuse has been reported to produce abnormalities earlier in the HIV process. Alcohol abuse and HIV infection also have additive effects on abnormal brain electrophysiological measurements. However, the relationship between the effects of alcohol and AIDS-related neuronal and cognitive dysfunction require further examination. The studies proposed will test the overall hypothesis that alcohol unmasks neuropsychological deficits in rhesus monkeys infected with simian immunodeficiency virus (SIV). This component will systematically explore the significant interaction that occurred between ethanol and SIV during behavioral testing in the previous funding period and begin to examine the potential role of GABAA and NMDA receptors in that interaction. An important aspect of this research will be the regimen for ethanol administration and the use of SIV, which will control for ethanol consumption in infected subjects while avoiding many uncontrolled variables that frequently compromise clinical studies with humans. These experiments will investigate whether chronic alcohol administration will 1) potentiate neuropsychological deficits produced by SIV in monkeys responding under a complex neuropsychological procedure such as repeated acquisition, 2) produce tolerance to the rate-decreasing and error-increasing effects of alcohol and cross tolerance to behavioral effects of three different, site-specific, positive GABAA modulators in both sham- and SIV-inoculated monkeys, 3) produce cross tolerance to behavioral effects of NMDA receptor antagonists in both sham- or SIV-inoculated monkeys, and 4) reduce effectiveness of antiviral therapy in SIV-infected monkeys. There are currently 16 animals enrolled on this study. Eight of the animals are undergoing neuropsychological testing and are administered alcohol 4 times weekly. The remaining eight animals are newly acquired and are being conditioned for the neuropsychological testing. Currently all 16 of the animals are niave, have not been infected with