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Effects of Genetic and Procedural Variation on Measurement of Alcohol Sensitivity in Mouse Inbred Strains

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Mice from eight inbred strains were studied for their acute sensitivity to ethanol as indexed by the degree of hypothermia (HT), indexed as the reduction from pre-injection baseline of their body temperature. Two weeks later, mice were tested for their loss of righting reflex (LRR) after a higher dose of ethanol. The LRR was tested using the “classical” method of watching for recovery in animals placed on their backs in a V-shaped trough and recording duration of LRR. In a separate test, naive animals of the same strains were tested for HT repeatedly to assess the development of rapid (RTOL) and chronic tolerance (CTOL). We have recently developed a new method for testing LRR that leads to a substantial increase in the sensitivity of the test. Strains also have been found to differ in the new LRR test, as well as in the development of acute functional tolerance (AFT) to this response. In addition, our laboratory has periodically published strain difference data on the older versions of the HT and LRR responses. The earlier tests used some of the exact substrains tested currently, while for some strains, different substrains (usually, Nih versus Jax) were tested. We examined correlations of strain means to see whether patterns of strain differences were stable across time and across different test variants assessing the same behavioral construct. HT strain sensitivity scores were generally highly correlated across a 10–23 years period and test variants. The CTOL to HT was well-correlated across studies, and was also genetically similar to RTOL. The AFT, however, was related to neither RTOL nor CTOL, although this may be because different phenotypic end points were compared. The LRR data, which included a variant of the classical test, were not as stable. Measures of LRR onset were reasonably well correlated, as were those taken at recovery (e.g., duration). However, the two types of measures of LRR sensitivity to ethanol appear to be tapping traits that differ genetically. Also, the pattern of genetic correlation between HT and LRR initially reported in 1983 was not seen in current and contemporaneous studies. In certain instances, substrain seems to matter little, while in others, substrains differed a great deal. These data are generally encouraging about the stability of genetic differences.

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Acknowledgments

These studies and the preparation of this manuscript were supported by NIH grants AA19760, AA12714, AA13519, NSERC grant 45825, the Mouse Phenome Project, and the Department of Veterans Affairs. Thanks to Christina J. Cotnam, Andy J. Cameron, Chia-Hua Yu, Jason P. Schlumbohm, Katie L. Mordarski, and Karyn L. Best for expert technical assistance with Experiments 1–3, and many former students and research assistants for help with the earlier work.

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Authors and Affiliations

  1. Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University, and VA Medical Center (R&D 12), 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA

    John C. Crabbe & Pamela Metten

  2. Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX, 78712, USA

    Igor Ponomarev

  3. Department of Psychology, University of Southern California, Los Angeles, CA, 90089, USA

    Carol A. Prescott

  4. Great Lakes Institute for Environmental Research, Department of Biological Sciences, University of Windsor, 401 Sunset Drive, Windsor, Ont., Canada, N9B 3P4

    Douglas Wahlsten

  5. VA Medical Center (R&D 12), 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA

    John C. Crabbe

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  1. John C. Crabbe
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  3. Igor Ponomarev
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Correspondence to John C. Crabbe.

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Crabbe, J.C., Metten, P., Ponomarev, I. et al. Effects of Genetic and Procedural Variation on Measurement of Alcohol Sensitivity in Mouse Inbred Strains. Behav Genet 36, 536–552 (2006). https://doi.org/10.1007/s10519-006-9067-6

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