Ethanol Metabolism and Osmolarity Modify Behavioral Responses to Ethanol in C. elegans
Article first published online: 6 APR 2012
Copyright © 2012 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 36, Issue 11, pages 1840–1850, November 2012
How to Cite
Alaimo, J. T., Davis, S. J., Song, S. S., Burnette, C. R., Grotewiel, M., Shelton, K. L., Pierce-Shimomura, J. T., Davies, A. G. and Bettinger, J. C. (2012), Ethanol Metabolism and Osmolarity Modify Behavioral Responses to Ethanol in C. elegans. Alcoholism: Clinical and Experimental Research, 36: 1840–1850. doi: 10.1111/j.1530-0277.2012.01799.x
- Issue published online: 29 OCT 2012
- Article first published online: 6 APR 2012
- Manuscript Accepted: 10 FEB 2012
- Manuscript Received: 10 JAN 2012
- NIH National Center for Research Support. Grant Number: 5T32AA007471
- Caenorhabditis elegans ;
- Alcohol Dehydrogenase;
- Aldehyde Dehydrogenase;
Ethanol (EtOH) is metabolized by a 2-step process in which alcohol dehydrogenase (ADH) oxidizes EtOH to acetaldehyde, which is further oxidized to acetate by aldehyde dehydrogenase (ALDH). Although variation in EtOH metabolism in humans strongly influences the propensity to chronically abuse alcohol, few data exist on the behavioral effects of altered EtOH metabolism. Here, we used the nematode Caenorhabditis elegans to directly examine how changes in EtOH metabolism alter behavioral responses to alcohol during an acute exposure. Additionally, we investigated EtOH solution osmolarity as a potential explanation for contrasting published data on C. elegans EtOH sensitivity.
We developed a gas chromatography assay and validated a spectrophotometric method to measure internal EtOH in EtOH-exposed worms. Further, we tested the effects of mutations in ADH and ALDH genes on EtOH tissue accumulation and behavioral sensitivity to the drug. Finally, we tested the effects of EtOH solution osmolarity on behavioral responses and tissue EtOH accumulation.
Only a small amount of exogenously applied EtOH accumulated in the tissues of C. elegans and consequently their tissue concentrations were similar to those that intoxicate humans. Independent inactivation of an ADH-encoding gene (sodh-1) or an ALDH-encoding gene (alh-6 or alh-13) increased the EtOH concentration in worms and caused hypersensitivity to the acute sedative effects of EtOH on locomotion. We also found that the sensitivity to the depressive effects of EtOH on locomotion is strongly influenced by the osmolarity of the exogenous EtOH solution.
Our results indicate that EtOH metabolism via ADH and ALDH has a statistically discernable but surprisingly minor influence on EtOH sedation and internal EtOH accumulation in worms. In contrast, the osmolarity of the medium in which EtOH is delivered to the animals has a more substantial effect on the observed sensitivity to EtOH.