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Ethanol Metabolism and Osmolarity Modify Behavioral Responses to Ethanol inC. elegans
| Content Provider | Scilit |
|---|---|
| Author | Alaimo, Joseph T. Davis, Scott J. Song, Sam S. Burnette, Christopher R. Grotewiel, Mike Shelton, Keith L. Pierce-Shimomura, Jonathan T. Davies, Andrew G. Bettinger, Jill C. |
| Copyright Year | 2012 |
| Description | Journal: Alcoholism: Clinical and Experimental Research Background Ethanol (E tOH ) is metabolized by a 2‐step process in which alcohol dehydrogenase (ADH ) oxidizes E tOH to acetaldehyde, which is further oxidized to acetate by aldehyde dehydrogenase (ALDH ). Although variation in E tOH metabolism in humans strongly influences the propensity to chronically abuse alcohol, few data exist on the behavioral effects of altered E tOH metabolism. Here, we used the nematode Caenorhabditis elegans to directly examine how changes in E tOH metabolism alter behavioral responses to alcohol during an acute exposure. Additionally, we investigated E tOH solution osmolarity as a potential explanation for contrasting published data on C. elegans E tOH sensitivity. Methods We developed a gas chromatography assay and validated a spectrophotometric method to measure internal E tOH in E tOH ‐exposed worms. Further, we tested the effects of mutations in ADH and ALDH genes on E tOH tissue accumulation and behavioral sensitivity to the drug. Finally, we tested the effects of E tOH solution osmolarity on behavioral responses and tissue E tOH accumulation. Results Only a small amount of exogenously applied E tOH 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 E tOH concentration in worms and caused hypersensitivity to the acute sedative effects of E tOH on locomotion. We also found that the sensitivity to the depressive effects of E tOH on locomotion is strongly influenced by the osmolarity of the exogenous E tOH solution. Conclusions Our results indicate that E tOH metabolism via ADH and ALDH has a statistically discernable but surprisingly minor influence on E tOH sedation and internal E tOH accumulation in worms. In contrast, the osmolarity of the medium in which E tOH is delivered to the animals has a more substantial effect on the observed sensitivity to E tOH . |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396773/pdf |
| Ending Page | 1850 |
| Page Count | 11 |
| Starting Page | 1840 |
| e-ISSN | 15300277 |
| DOI | 10.1111/j.1530-0277.2012.01799.x |
| Journal | Alcoholism: Clinical and Experimental Research |
| Issue Number | 11 |
| Volume Number | 36 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2012-04-06 |
| Access Restriction | Open |
| Subject Keyword | Journal: Alcoholism: Clinical and Experimental Research Substance Abuse Caenorhabditis Elegans Alcohol Dehydrogenase Aldehyde Dehydrogenase |
| Content Type | Text |
| Resource Type | Article |
