Abstract

The effects of ethanol exposure on mammalian central nervous system function will be pursued using both extracellular and intracellular recording in the intact brain in situ, in the in vitro brain slice and in intraocular brain transplants. Studies will focus on genetic variants manifesting differential alcohol-related behaviors as model systems for examining acute ethanol actions as well as for studying tolerance and dependence to alcohol. The long-term objectives of this research program are three fold. First, the mechanism of electrophysiological responses to ethanol will be characterized as direct, modulatory or involving local circuit interneurons. Second, changes in responses to ethanol, as well as functional changes in neurotransmitter systems will be determined after induction of tolerance or dependence. Finally, the genetic variants will permit ethanol-induced electrophysiological responses to be correlated with alcohol-induced behaviors. A greater understanding of how ethanol alters CNS function should furnish new insights into the problems of alcohol intoxication and alcoholism.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA005915-06
Application #
3109196
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1983-07-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Backman, C; West, J R; Mahoney, J C et al. (1998) Electrophysiological characterization of cerebellar neurons from adult rats exposed to ethanol during development. Alcohol Clin Exp Res 22:1137-45
Freund, R K; Palmer, M R (1997) Beta adrenergic sensitization of gamma-aminobutyric acid receptors to ethanol involves a cyclic AMP/protein kinase A second-messenger mechanism. J Pharmacol Exp Ther 280:1192-200
Lin, A M; Bickford, P C; Palmer, M R et al. (1997) Effects of ethanol and nomifensine on NE clearance in the cerebellum of young and aged Fischer 344 rats. Brain Res 756:287-92
Freund, R K; Palmer, M R (1997) Ethanol depression of cerebellar Purkinje neuron firing involves nicotinic acetylcholine receptors. Exp Neurol 143:319-22
Trok, K; Palmer, M R; Freund, R K et al. (1997) Functional interactions between spinal cord grafts suggest asymmetries dictated by graft maturity. Exp Neurol 145:268-77
Pearson, B J; Donatelli, D P; Freund, R K et al. (1997) Differential development and characterization of rapid acute neuronal tolerance to the depressant effects of ethanol on cerebellar Purkinje neurons of low-alcohol-sensitive and high-alcohol-sensitive rats. J Pharmacol Exp Ther 280:739-46
Freund, R K; Palmer, M R (1996) 8-Bromo-cAMP mimics beta-adrenergic sensitization of GABA responses to ethanol in cerebellar Purkinje neurons in vivo. Alcohol Clin Exp Res 20:408-12
Inoue, H K; Henschen, A; Olson, L (1994) Human fetal spinal cord xenografted to the eye of athymic nude rats: survival, ultrastructural differentiation, glial responses and vascular interactions. J Electron Microsc (Tokyo) 43:1-9
Lin, A M; Freund, R K; Hoffer, B J et al. (1994) Ethanol-induced depressions of cerebellar Purkinje neurons are potentiated by beta-adrenergic mechanisms in rat brain. J Pharmacol Exp Ther 271:1175-80
Freund, R K; Wang, Y; Palmer, M R (1993) Differential effects of ethanol on the firing rates of Golgi-like neurons and Purkinje neurons in cerebellar slices in vitro. Neurosci Lett 164:9-12

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