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Genetic Relationship Between Predisposition for Binge Alcohol Consumption and Blunted Sensitivity to Adverse Effects of Alcohol in Mice
Author(s) -
Fritz Brandon M.,
Cordero Kristy A.,
BarkleyLevenson Amanda M.,
Metten Pamela,
Crabbe John C.,
Boehm Stephen L.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12385
Subject(s) - ethanol , alcohol , ataxia , hypnotic , chemistry , medicine , endocrinology , adverse effect , anesthesia , psychology , biochemistry , psychiatry
Background Initial sensitivity to ethanol (EtOH) and the capacity to develop acute functional tolerance ( AFT ) to its adverse effects may influence the amount of alcohol consumed and may also predict future alcohol use patterns. The current study assessed sensitivity and AFT to the ataxic and hypnotic effects of EtOH in the first replicate of mice ( HDID ‐1) selectively bred for high blood EtOH concentrations ( BEC s) following limited access to EtOH in the Drinking in the Dark ( DID ) paradigm. Methods Naïve male and female HDID ‐1 and HS /Npt mice from the progenitor stock were evaluated in 3 separate experiments. In Experiments 1 and 2, EtOH‐induced ataxia was assessed using the static dowel task. In Experiment 3, EtOH‐induced hypnosis was assessed by using modified restraint tubes to measure the loss of righting reflex ( LORR ). Results HDID ‐1 mice exhibited reduced initial sensitivity to both EtOH‐induced ataxia ( p < 0.001) and hypnosis ( p < 0.05) relative to HS /Npt mice. AFT was calculated by subtracting the BEC at loss of function from the BEC at recovery (Experiments 1 and 3) or by subtracting BEC at an initial recovery from the BEC at a second recovery following an additional alcohol dose (Experiment 2). The dowel test yielded no line differences in AFT , but HS /Npt mice developed slightly greater AFT to EtOH‐induced LORR than HDID ‐1 ( p < 0.05). Conclusions These results suggest that HDID ‐1 mice exhibit aspects of blunted ataxic and hypnotic sensitivity to EtOH which may influence their high EtOH intake via DID , but do not display widely different development of AFT . These findings differ from previous findings with the high alcohol‐preferring ( HAP ) selected mouse lines, suggesting that genetic predisposition for binge, versus other forms of excessive alcohol consumption, is associated with unique responses to EtOH‐induced motor incoordination.