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Pharmacology and Neuroscience

1)The broad objective of the proposed study is to establish the methods and procedures required to demonstrate our ability to conduct experiments in mice on the effects of alcohol on CNS infection by the vesicular stomatitis virus (VSV). The hypothesis to be tested is that alcohol can have detrimental effects by suppression of innate CNS immunity during viral infection, specifically inhibition of nitric oxide production by reduced iNOS expression. 2) The general methods to be used include growth of VSV and isolation of infectious �B� particles; determination of VSV titers; inoculation of mice with VSV; control and alcohol treatment of mice; serum nitrate and nitrite determinations, tissue inducible nitric oxide synthase (iNOS) Western blots, and immunohistochemistry for VSV proteins. 3) Suppression of inducible genes such as Nos2 that are involved in host responses to brain injuries such as infection and trauma may have dire consequences during acute binge drinking or chronic alcohol abuse. It is well established that alcohol abusers are more prone to opportunistic pathogens than non-abusers. However, there is a paucity of information regarding alcohol�s effects on neurotropic pathogens and their consequences in alcohol abusers, including individuals infected with HIV. Studies proposed in this application will provide preliminary data on the consequences of alcohol use in CNS viral infections that may have direct relevance to the development of AIDS dementia and other CNS disorders.