Abstract

The objective of this investigation will be to determine the central nervous system membrane alterations produced by acute and chronic ethanol and barbiturate administratiaon which occur in a correlative manner to intoxication and the development of tolerance and physical dependence. Specifically, male, Sprague-Dawley rats will be separated into the following treatment groups: control, pairfed control, tolerant, withdrawn and recovered. Whole brains and brain regions (cerebral cortex, cerebellu, brain stem, hypothalamus, midbrain and corpus striatum) will be removed from animals in each treatment group and synaptosomes, synaptosomal plasma membranes (SPM) mitochondria and microsomes will be isolated by ultracentrifugation. Synaptosomes from each treatment group and each brain region will be analyzed for 1) cross-tolerance to barbiturate-and ethanol-induced inhibition of 45Ca++ transport produced by acidic membrane lipids after acute and/or chronic administration of these drugs. In addition, the acute and chronic effects of ethanol and barbiturates will be examined on ATP-dependent 45Ca++ uptake and fatty acid composition of the subcellular organelles listed above. The overall objective will be to determine cellular mechanisms involved in the production of sedation and the deeelopment of tolerance and physical dependence.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA005809-04
Application #
3109085
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1982-07-01
Project End
1985-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Texas Austin
Department
Type
Schools of Pharmacy
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78713

  Publications

Morrow, A Leslie; Ferrani-Kile, Karima; Davis, Margaret I et al. (2004) Ethanol effects on cell signaling mechanisms. Alcohol Clin Exp Res 28:217-27
Acquaah-Mensah, George K; Kehrer, James P; Leslie, Steven W (2002) In utero ethanol suppresses cerebellar activator protein-1 and nuclear factor-kappa B transcriptional activation in a rat fetal alcohol syndrome model. J Pharmacol Exp Ther 301:277-83
Acquaah-Mensah, G K; Leslie, S W; Kehrer, J P (2001) Acute exposure of cerebellar granule neurons to ethanol suppresses stress-activated protein kinase-1 and concomitantly induces AP-1. Toxicol Appl Pharmacol 175:10-8
Spuhler-Phillips, K; Lee, Y H; Hughes, P et al. (1997) Effects of prenatal ethanol exposure on brain region NMDA-mediated increase in intracellular calcium and the NMDAR1 subunit in forebrain. Alcohol Clin Exp Res 21:68-75
Lee, Y H; Spuhler-Phillips, K; Randall, P K et al. (1996) Effects of prenatal ethanol exposure on voltage-dependent calcium entry into neonatal whole brain-dissociated neurons. Alcohol Clin Exp Res 20:921-8
Lee, Y H; Spuhler-Phillips, K; Randall, P K et al. (1994) Effects of prenatal ethanol exposure on N-methyl-D-aspartate-mediated calcium entry into dissociated neurons. J Pharmacol Exp Ther 271:1291-8
Weaver, M S; Lee, Y H; Morris, J L et al. (1993) Effects of in vitro ethanol and fetal ethanol exposure on glutathione stimulation of N-methyl-D-aspartate receptor function. Alcohol Clin Exp Res 17:643-50
Brown, L M; Sims, J S; Randall, P et al. (1993) Omega-conotoxin increases sleep time following ethanol injection. Alcohol 10:159-62
Leslie, S W; Brown, L M; Trent, R D et al. (1992) Stimulation of N-methyl-D-aspartate receptor-mediated calcium entry into dissociated neurons by reduced and oxidized glutathione. Mol Pharmacol 41:308-14
Brown, L M; Trent, R D; Jones, T W et al. (1992) Alcohol inhibition of NMDA-stimulated catecholamine efflux in aging brain. Alcohol 9:555-8

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