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Construction of Vapor Chambers Used to Expose Mice to Alcohol During the Equivalent of all Three Trimesters of Human Development
Published on: July 13, 2014
Alcohol withdrawal severity in inbred mouse (Mus musculus) strains
1Portland Alcohol Research Center, Veterans Affairs Medical Center, Portland, OR 97239, USA. mettenp@ohsu.edu
Abstract:
Male mice (Mus musculus) from 15 standard inbred strains were exposed to a nearly constant concentration of ethanol (EtOH) vapor for 72 hr, averaging 1.59 +/- 0.03 mg EtOH/mL blood at withdrawal. EtOH- and air-exposed groups were tested hourly for handling-induced convulsions for 10 hr and at Hours 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of control values), and by design these differences were independent of strain differences in EtOH metabolism. Correlation of strain mean withdrawal severity with other responses to EtOH supported previously reported genetic relationships of high EtOH withdrawal with low drinking, high conditioned taste aversion, low tolerance to EtOH-induced hypothermia, and high stimulated activity after low-dose EtOH. Also supported were the positive genetic correlations among EtOH, barbiturate, and benzodiazepine withdrawal. Sensitivity of naive mice to several chemical convulsant-induced seizures was also correlated with EtOH withdrawal.
Insights
Genetic factors significantly influence alcohol (ethanol) withdrawal severity in mice. Different inbred strains exhibit varied responses, linking withdrawal to other alcohol-related behaviors and sensitivities.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Alcohol withdrawal syndrome (AWS) is a significant clinical concern.
- Genetic factors play a crucial role in AWS variability.
- Understanding these genetic underpinnings can inform treatment strategies.
Purpose of the Study:
- To investigate genetic influences on ethanol withdrawal severity in mice.
- To explore correlations between ethanol withdrawal and other alcohol-related phenotypes.
- To examine the relationship between ethanol withdrawal and sensitivity to other convulsants.
Main Methods:
- Exposed 15 inbred mouse strains to ethanol vapor for 72 hours.
- Assessed handling-induced convulsions during withdrawal.
- Measured ethanol metabolism and other alcohol responses.
Main Results:
- Marked strain differences in ethanol withdrawal severity were observed.
- Withdrawal severity was independent of ethanol metabolism rates.
- High withdrawal correlated with low drinking, high taste aversion, low hypothermia tolerance, and high activity.
Conclusions:
- Genetic background strongly dictates ethanol withdrawal severity in mice.
- Ethanol withdrawal shares genetic correlations with other substance use behaviors and sensitivities.
- Findings support a common genetic basis for withdrawal syndromes across different drugs.
