NRSA Fellowship/Self: Ethanol Withdrawal, HIV-1, and Corticosterone

Alcohol-withdrawal induced neurotoxicity and viable options for its treatment have not yet been fully elucidated However, research indicates a role for polyamine-sensitive sites on the NMDA receptor (NMDAr) system and glucocorticoids in ethanol withdrawal (EWD)-induced neurodegeneration. Further, estimates indicate that -75% of HIV-positive individuals fulfill DSM-IV criteria for alcohol and/or substance abuse. Excessive glucocorticoid release has also been shown to exacerbate certain health problems, including those that contribute to neurodegeneration. Therefore, these studies will examine the role of glutamate and corticosteroid receptors in mediating the superadditive neurotoxic effects of ethanol withdrawal and the HIV- 1 viral protein Tat. For these experiments, adolescent rats will implanted with intra-hippocampal cannula into the CA1 region via stereotaxic surgery. The animals will then be chronically exposed to ethanol and undergo withdrawal, with or without co-exposure to Tat. A subsequent study will investigate the efficacy of novel NMDAr polyamine-site and glucocorticoid receptor antagonists in blocking any resultant neurotoxicity. Brains will be ex1racted and examined for damage via immunohistochemistry and autoradiographic imaging.