The goal of the proposed research is to explore the extent and mechanism of the antagonistic effect of low level hyperbaric environments on ethanol intoxication. Experiments will be conducted in mice using sleep-time, rectal temperature, respiratory rate, mortality and signs of physical dependence as measures of the antagonistic interaction between ethanol and low level hyperbaric environments. These experiments will: (1) Determine the generality of the antagonism across strains and species; (2) Investigate the extent of the antagonism at different ethanol doses; (3) Outline the time-course of the antagonism; (4) Explore the mechanism of the antagonism. It is felt that these studies will provide further insights about the mechanism(s) by which ethanol affects the brain and behavior and may provide a useful ethanol antagonist.
| Wyatt, Letisha R; Finn, Deborah A; Khoja, Sheraz et al. (2014) Contribution of P2X4 receptors to ethanol intake in male C57BL/6 mice. Neurochem Res 39:1127-39 |
| Popova, Maya; Trudell, James; Li, Kaixun et al. (2013) Tryptophan 46 is a site for ethanol and ivermectin action in P2X4 receptors. Purinergic Signal 9:621-32 |
| Perkins, Daya I; Trudell, James R; Asatryan, Liana et al. (2012) Charge and geometry of residues in the loop 2 ? hairpin differentially affect agonist and ethanol sensitivity in glycine receptors. J Pharmacol Exp Ther 341:543-51 |
| Ostrovskaya, Olga; Asatryan, Liana; Wyatt, Letisha et al. (2011) Ethanol is a fast channel inhibitor of P2X4 receptors. J Pharmacol Exp Ther 337:171-9 |
| Popova, Maya; Asatryan, Liana; Ostrovskaya, Olga et al. (2010) A point mutation in the ectodomain-transmembrane 2 interface eliminates the inhibitory effects of ethanol in P2X4 receptors. J Neurochem 112:307-17 |
| Perkins, Daya I; Trudell, James R; Crawford, Daniel K et al. (2010) Molecular targets and mechanisms for ethanol action in glycine receptors. Pharmacol Ther 127:53-65 |
| Asatryan, Liana; Popova, Maya; Perkins, Daya et al. (2010) Ivermectin antagonizes ethanol inhibition in purinergic P2X4 receptors. J Pharmacol Exp Ther 334:720-8 |
| Perkins, Daya I; Trudell, James R; Crawford, Daniel K et al. (2009) Loop 2 structure in glycine and GABA(A) receptors plays a key role in determining ethanol sensitivity. J Biol Chem 284:27304-14 |
| Perkins, Daya I; Trudell, James R; Crawford, Daniel K et al. (2008) Targets for ethanol action and antagonism in loop 2 of the extracellular domain of glycine receptors. J Neurochem 106:1337-49 |
| Crawford, Daniel K; Perkins, Daya I; Trudell, James R et al. (2008) Roles for loop 2 residues of alpha1 glycine receptors in agonist activation. J Biol Chem 283:27698-706 |
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