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 produces 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 are still poorly understood and require further examination. The studies proposed in this research component will test the overall hypothesis that alcohol unmasks neuropsychological deficits in rhesus monkeys infected with simian immunodeficiency virus (SIV). More specifically, 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. In particular, these experiments will investigate whether chronic alcohol administration will 1) potentiate the 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 the behavioral effects of three different, site-specific, positive GABAA modulators in both sham- and SIV-inoculated monkeys, 3) produce cross tolerance to the behavioral effects of NMDA receptor antagonists in both sham- or SIV-inoculated monkeys, and 4) reduce the effectiveness of antiviral therapy in SIV-infected monkeys.
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