Abstract

Research described in this application will assess the mechanisms by which ascorbate modulates neostriatal neuronal activity. Possible interactions with dopamine or glutamate will be assessed in behaviorally distinct neuronal populations. The effects of ascorbate pretreatment on dopamine-mediated behavioral responses will be examined in parallel studies using simultaneous voltammetric procedures to obtain quantitative data on real-time neostriatal ascorbate release. Attention will center on the ability of ascorbate to alter open-field behavioral activity induced by dopamine agonists as well as performance on a lever-release conditioned avoidance response task known to depend on neostriatal dopamine transmission. A separate line of investigation will combine voltammetry with intracerebral infusions of glutamate or dopamine agonists to identify the processes underlying the ability of haloperidol, a neuroleptic and dopamine antagonist, to enhance neostriatal ascorbate release during long-term treatment.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS035663-04
Application #
2892138
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Michel, Mary E
Project Start
1996-07-01
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2001-06-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Indiana University Bloomington
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401

  Publications

Nakhnikian, Alexander; Rebec, George V; Grasse, Leslie M et al. (2014) Behavior modulates effective connectivity between cortex and striatum. PLoS One 9:e89443
Rebec, George V (2013) Dysregulation of corticostriatal ascorbate release and glutamate uptake in transgenic models of Huntington's disease. Antioxid Redox Signal 19:2115-28
Estrada-Sánchez, Ana María; Barton, Scott J; Burroughs, Courtney L et al. (2013) Dysregulated striatal neuronal processing and impaired motor behavior in mice lacking huntingtin interacting protein 14 (HIP14). PLoS One 8:e84537
Hong, S Lee; Rebec, George V (2012) Biological sources of inflexibility in brain and behavior with aging and neurodegenerative diseases. Front Syst Neurosci 6:77
Hong, S Lee; Cossyleon, Desirée; Hussain, Wajeeha A et al. (2012) Dysfunctional behavioral modulation of corticostriatal communication in the R6/2 mouse model of Huntington's disease. PLoS One 7:e47026
Miller, Benjamin R; Dorner, Jenelle L; Bunner, Kendra D et al. (2012) Up-regulation of GLT1 reverses the deficit in cortically evoked striatal ascorbate efflux in the R6/2 mouse model of Huntington's disease. J Neurochem 121:629-38
Murphy-Nakhnikian, Alexander; Dorner, Jenelle L; Fischer, Benjamin I et al. (2012) Abnormal burst patterns of single neurons recorded in the substantia nigra reticulata of behaving 140 CAG Huntington's disease mice. Neurosci Lett 512:1-5
Hong, S Lee; Barton, Scott J; Rebec, George V (2012) Neural correlates of unpredictability in behavioral patterns of wild-type and R6/2 mice. Commun Integr Biol 5:259-61
Estrada-Sánchez, Ana María; Rebec, George V (2012) Corticostriatal dysfunction and glutamate transporter 1 (GLT1) in Huntington's disease: interactions between neurons and astrocytes. Basal Ganglia 2:57-66
Hong, S Lee; Barton, Scott J; Rebec, George V (2012) Altered neural and behavioral dynamics in Huntington's disease: an entropy conservation approach. PLoS One 7:e30879

Showing the most recent 10 out of 33 publications