Abstract

This is a second resubmission of a competing renewal application, following three years of initial support. The applicant has determined that hippocampal LTP is ethanol sensitive. NMDA receptors seem to play a clear role in this sensitivity. However, inhibition of LTP by 100 mM ethanol exceeds that produced by inhibition of NMDA receptors by other pharmacological agents, leading to the hypothesis that an additional component of the inhibition may result from a ethanol's effects on GABAA receptors. This proposal further explores the actions of ethanol on NMDA receptor function, as well as probing the contribution and nature of GABAA receptors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA009675-06
Application #
6136994
Study Section
Special Emphasis Panel (ZRG4-ALTX-3 (01))
Project Start
1993-09-30
Project End
2002-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
6
Fiscal Year
2000
Total Cost
$146,848
Indirect Cost

  Institution

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

  Publications

Hicklin, Tianna R; Wu, Peter H; Radcliffe, Richard A et al. (2011) Alcohol inhibition of the NMDA receptor function, long-term potentiation, and fear learning requires striatal-enriched protein tyrosine phosphatase. Proc Natl Acad Sci U S A 108:6650-5
Goebel-Goody, S M; Davies, K D; Alvestad Linger, R M et al. (2009) Phospho-regulation of synaptic and extrasynaptic N-methyl-d-aspartate receptors in adult hippocampal slices. Neuroscience 158:1446-59
Davies, Kurtis D; Goebel-Goody, Susan M; Coultrap, Steven J et al. (2008) Long term synaptic depression that is associated with GluR1 dephosphorylation but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor internalization. J Biol Chem 283:33138-46
Davies, Kurtis D; Alvestad, Rachel M; Coultrap, Steven J et al. (2007) alphaCaMKII autophosphorylation levels differ depending on subcellular localization. Brain Res 1158:39-49
Coultrap, Steven J; Nixon, Kristin M; Alvestad, Rachel M et al. (2005) Differential expression of NMDA receptor subunits and splice variants among the CA1, CA3 and dentate gyrus of the adult rat. Brain Res Mol Brain Res 135:104-11
Goebel, Susan M; Alvestad, Rachel M; Coultrap, Steven J et al. (2005) Tyrosine phosphorylation of the N-methyl-D-aspartate receptor is enhanced in synaptic membrane fractions of the adult rat hippocampus. Brain Res Mol Brain Res 142:65-79
Alvestad, Rachel M; Grosshans, David R; Coultrap, Steven J et al. (2003) Tyrosine dephosphorylation and ethanol inhibition of N-Methyl-D-aspartate receptor function. J Biol Chem 278:11020-5
Grosshans, D R; Clayton, D A; Coultrap, S J et al. (2002) LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1. Nat Neurosci 5:27-33
Grosshans, D R; Browning, M D (2001) Protein kinase C activation induces tyrosine phosphorylation of the NR2A and NR2B subunits of the NMDA receptor. J Neurochem 76:737-44
Valenzuela, C F; Cardoso, R A; Lickteig, R et al. (1998) Acute effects of ethanol on recombinant kainate receptors: lack of role of protein phosphorylation. Alcohol Clin Exp Res 22:1292-9

Showing the most recent 10 out of 12 publications