The research career award (RCA/K02) plan outlined in this proposal will serve as a logical extension and critical support of my research career development in Women's Health/Drug Abuse at the University of Kentucky. Specifically, I propose to obtain additional training in order to extend my NIDA-funded research concerning intravenous drug abuse (IDU) in females to include HIV in the model. Such a cross-disciplinary effort is essential, as IDU is a major risk factor for HIV infection. Women IDU represent the fastest growing population of HIV positive individuals in the US. Currently, there is a paucity of neuroscientists with training in neurovirology and drug abuse models. Release time from teaching duties generated by this RCA will allow me the opportunity for a period of intensive research focus on IDU and HIV neurobiology. This training will strengthen my research efforts in this fast growing area by allowing me to work with infectious HIV+ cells and tissues. The specific research program proposed in this application is part of two NIDA funded R01 projects which together pose the major question: Are biological gender differences in responsiveness to (repeated) cocaine predisposing females to HIV-induced neurotoxicity? The hypothesis is: Estrogens will act as protective agents for the combined effects of repeated IV cocaine administration and gp120/Tat neurotoxicity. In this project, first, we will determine whether steroid hormones are neuroprotective against the combined effects of gp120/Tat and cocaine in cultured human fetal neurons. Second, I plan to extend our rodent model into work with human HIV+ brain tissue. These proposed studies will contribute to the scientific development of the applicant in the area of women's health and drug abuse and further our knowledge with regard to HIV neurotoxicity in this population. This training is essential to my research career progression (as rats do not develop AIDS) and this RCA will allow me the release time to critically test my research hypothesis in AIDS brain tissue from male and female drug abusers.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
1K02DA014401-01
Application #
6382970
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Frankenheim, Jerry
Project Start
2001-07-10
Project End
2002-06-30
Budget Start
2001-07-10
Budget End
2002-06-30
Support Year
1
Fiscal Year
2001
Total Cost
$76,217
Indirect Cost
Name
University of Kentucky
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Moran, Landhing M; Fitting, Sylvia; Booze, Rosemarie M et al. (2014) Neonatal intrahippocampal HIV-1 protein Tat(1-86) injection: neurobehavioral alterations in the absence of increased inflammatory cytokine activation. Int J Dev Neurosci 38:195-203
Patel, Dhyanesh Arvind; Booze, Rosemarie M; Mactutus, Charles F (2012) Prenatal cocaine exposure alters progenitor cell markers in the subventricular zone of the adult rat brain. Int J Dev Neurosci 30:1-9
Ferris, Mark J; Frederick-Duus, Danielle; Fadel, Jim et al. (2010) Hyperdopaminergic tone in HIV-1 protein treated rats and cocaine sensitization. J Neurochem 115:885-96
Fitting, Sylvia; Booze, Rosemarie M; Hasselrot, Ulla et al. (2010) Dose-dependent long-term effects of Tat in the rat hippocampal formation: a design-based stereological study. Hippocampus 20:469-80
Ferris, Mark J; Frederick-Duus, Danielle; Fadel, Jim et al. (2009) In vivo microdialysis in awake, freely moving rats demonstrates HIV-1 Tat-induced alterations in dopamine transmission. Synapse 63:181-5
Ferris, M J; Frederick-Duus, D; Fadel, J et al. (2009) The human immunodeficiency virus-1-associated protein, Tat1-86, impairs dopamine transporters and interacts with cocaine to reduce nerve terminal function: a no-net-flux microdialysis study. Neuroscience 159:1292-9
Fitting, Sylvia; Booze, Rosemarie M; Mactutus, Charles F (2008) Neonatal intrahippocampal injection of the HIV-1 proteins gp120 and Tat: differential effects on behavior and the relationship to stereological hippocampal measures. Brain Res 1232:139-54
Ferris, Mark J; Mactutus, Charles F; Booze, Rosemarie M (2008) Neurotoxic profiles of HIV, psychostimulant drugs of abuse, and their concerted effect on the brain: current status of dopamine system vulnerability in NeuroAIDS. Neurosci Biobehav Rev 32:883-909
Fitting, Sylvia; Booze, Rosemarie M; Gilbert, Candace A et al. (2008) Effects of chronic adult dietary restriction on spatial learning in the aged F344 x BN hybrid F1 rat. Physiol Behav 93:560-9
Fitting, Sylvia; Booze, Rosemarie M; Hasselrot, Ulla et al. (2008) Differential long-term neurotoxicity of HIV-1 proteins in the rat hippocampal formation: a design-based stereological study. Hippocampus 18:135-47

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